Search

Throughout the COVID-19 pandemic, pregnant women have been classified as a vulnerable population. However, the evidence on the effect of infection during pregnancy on maternal and neonatal outcomes is still uncertain, and related research comprising a large population of pregnant women in Asian countries is limited. We constructed a national cohort including mothers and children (369,887 pairs) registered in the Prevention Agency-COVID-19-National Health Insurance Service (COV-N), from January 1, 2020 to March 31, 2022. We performed propensity score matchings and generalized estimation equation models to estimate the effect of COVID-19 on maternal and neonatal outcomes. In summary, we found little evidence of the effect of COVID-19 infection during pregnancy on maternal and neonatal outcomes; however, a relationship between COVID-19 infection in the second trimester and postpartum hemorrhages was discovered (Odds ratio (OR) of Delta period: 2.26, 95% Confidence intervals (CI): 1.26, 4.05). In addition, neonatal intensive care unit (NICU) admissions increased due to COVID-19 infection (pre-Delta period: 2.31, 95% CI: 1.31, 4.10; Delta period: 1.99, 95% CI: 1.47, 2.69; Omicron period: 2.36, 95% CI: 1.75, 3.18). Based on the national retrospective cohort study data, this study investigated the effects of COVID-19 infection on maternal and neonatal outcomes in Korea from the pre-Delta to the initial Omicron epidemic periods. Our evidence suggests that the timely and successful policies of the government and academia in response to COVID-19 infections in newborns in Korea may cause an increase in NICU admissions, but nonetheless, they prevent adverse maternal and neonatal outcomes simultaneously.

Background: VACTERL association is a widely known congenital malformation that includes vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Patients with VACTERL and hydrocephalus appear to form a distinct group, both genetically and phenotypically, and their condition has been called VACTERL-H syndrome. Most cases of VACTERL-H have been reported postnatally, as VACTER-H syndrome is difficult to diagnose prenatally. Case Presentation: Here, we report a case of VACTERL-H syndrome in a dichorionic and diamniotic twin diagnosed prenatally by ultrasonography and confirmed postnatally by three-dimensional computed tomography (3D CT). A 34-year-old multiparous female was referred to our institution at 31 + 3 weeks gestation for suspected fetal ventriculomegaly. Detailed examinations using two-dimensional and Doppler ultrasounds revealed hydrocephalus, bilateral dysplastic upper arms, radial aplasia, unilateral pulmonary agenesis, dextrocardia with right atrial enlargement, a unilateral hypoplastic ectopic kidney, a single umbilical artery, a tracheoesophageal fistula with a small stomach, polyhydramnios, and anal atresia. Findings from the postnatal 3D CT aligned with the prenatal diagnosis, showing upper-limb agenesis, dextrocardia with pulmonary hypoplasia, tracheoesophageal fistula, imperforate anus, and colon dilatation. The affected 1390-g male twin had an unaffected 1890-g female twin sister and a healthy 6-year-old brother. Conclusions: Upon encountering fetuses with multiple anomalies, including ventriculomegaly, a small stomach with polyhydramnios, an abnormally positioned heart, and upper-limb abnormalities, clinicians should perform systematic ultrasonographic examinations to detect associated anomalies and be aware of VACTERL-H syndrome.

Background: Atrial flutter is an infrequent yet potentially fatal arrhythmia. Digoxin is the preferred first-line treatment for fetal atrial flutter due to its efficacy and favorable safety profile. The optimal digoxin serum target level for neonatal atrial flutter management remains uncertain, with the standard target level ranging from 1.0 to 2.0 ng/mL due to potential toxicity concerns above this threshold. Case Presentation: We present a case of atrial flutter in a fetus within a monochorionic diamniotic (MCDA) twin pregnancy that was successfully managed using a higher-than-standard target level of digoxin. A 34-year-old nulliparous woman was referred to our institution at 31 + 3 weeks of gestation due to fetal distress in an MCDA twin pregnancy. Fetal echocardiography revealed a ventricular rate of 214 bpm in twin A, while twin B exhibited no abnormal findings. Conclusions: Our case highlights a distinct correlation between the serum digoxin level and its impact on atrial flutter. A higher target serum level of digoxin may be necessary to achieve sinus conversion due to the unique maternal and fetal circulatory characteristics in MCDA pregnancies.

The objective of this study is to determine whether the parent-child relationship exerts a mediating effect on the influencing relationship of the self-concept of children and adolescents with career maturity. To this end, we processed data from 5621 students who participated in the first through fifth rounds of the survey in the 2013 Korea Education Longitudinal Study. We performed a paired sample t-test to verify differences between the groups of children and adolescents. To verify the mediating effect of the parent-child relationship on the influencing relationship of self-concept among children and adolescents with career maturity. The results showed that there was a difference depending on gender and city size in terms of self-concept, career maturity, and relationship. This study also revealed a significant discrepancy in the self-concept and parent-child relationship based on the developmental stages. In addition, the study also verified the mediating effect of the parent-child relationship in the relationship between the self-concept of children and adolescents and their career maturity. Based on these findings, it is necessary to implement a systematic education program for parents because the parent-child relationship is highly important in improving students' career maturity.

Background/purpose: The purpose of this study was to develop and validate the Learning Leader Competency Test in South Korean university students. Based on the analysis of previous studies, this study defined the concept of learning leader competencies, consisting of cognitive, motivational, and behavioral domains. Materials/methods. A total of 638 university students participated in the study and data were collected via online survey. Exploratory factor analysis was conducted using principal axis factoring and Oblimin rotation. Confirmatory factor analysis was performed using maximum likelihood and goodness indices such as IFI, TLI, CFI and RMSEA. Construct, convergent, discriminant, and cross-validities were tested. Results: The Learning Leader Competency Test consists of 23 items and three factors; knowledge, thinking, and problem solving; learning goal orientation and self-determination; and constructive self-expectation and caring for the community. The test's reliability (Cronbach's [alpha] = 0.856) and validity were confirmed. Conclusion: This study defines the concept of learning leader competency and identifies the subcomponents of learning leader competency into the cognitive, motivational, and behavioral domains. This test may be applied in order to determine the extent to which university students possess the competency of becoming a leader in learning.

Background: Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome, also known as Herlyn-Werner-Wunderlich syndrome, is a rare syndrome characterized by the triad of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Most cases of OHVIRA have been reported in adolescents or adults. Gartner duct cysts, including those manifesting as vaginal wall cysts, are also rare. Fetal OHVIRA syndrome and Gartner duct cysts are difficult to diagnose. Case Presentation: Here, the authors report a case of combined OHVIRA and Gartner duct cyst diagnosed prenatally by ultrasonography, along with a brief review of the relevant published reports. A 30-year-old nulliparous female was referred to our institution at 32 weeks’ gestation for fetal right kidney agenesis. Detailed ultrasonographic examinations using 2D, 3D, and Doppler ultrasounds revealed hydrocolpometra, and uterus didelphys, with a normal anus and right kidney agenesis. Conclusions: When encountering female fetuses with ipsilateral renal agenesis or vaginal cysts, clinicians should be aware of OHVIRA syndrome and Gartner duct cysts and perform systematic ultrasonographic examinations for other genitourinary anomalies.

This study aimed to design a task in an everyday context to support high school students' exploration of the truth values of propositional conditionals and to understand their difficulties. The results showed that students could identify that the truth value of a propositional conditional is determined by two variables (the truth values of the antecedent and the consequent) while organizing the propositional conditionals generated from the open sentence and that a social contract situation can help students understand why the truth value of a conditional with a false antecedent is true. The study also revealed that students' difficulties in determining the truth values of conditionals are closely related to the time variable in an everyday context and the confusion between conditionals and causality. The findings from this study on the strategy and difficulties exhibited by students when determining the truth value of everyday conditional sentences can inform future efforts to teach formal mathematics in real-world contexts.

This study investigated the influence of South Korean university students' contact experiences with North Korean refugee university students on social identity and integrated conflicts. The study was conducted with students in years 1-4 of university enrolled in S University in Seoul. Data from 446 participants were gathered. Pearson's correlation analysis was conducted to determine the relationship between college students' contact experience with North Korean defector students, with variables of social identity and integrated conflict included. In addition, a t-test was conducted to analyse the differences in social identities and integrated conflicts according to whether or not college students participated in a unification leadership camp and whether or not they attended lectures related to unification. This study found significant correlations between variables such as contact experience, social identity and integrated conflicts. In addition, an increase in experiences between North Korean defectors and South Korean university students had a positive effect on social identity and negatively affected integrative conflict. In addition, there was no difference in social identity and integrated conflicts according to whether or not students participated in the Unification Camp or attended lectures related to unification. The results of this study will contribute to the development of programs and course openings to increase social identity and reduce integrated conflicts by expanding the contact experience between South and North Korean college students.

As the proportion of multicultural family increases in Korea, there has been an acceleration in the emergence of a multicultural and multiracial society, resulting in more students with different cultural backgrounds in schools. Therefore, it is necessary to achieve harmony and integration among people from various cultures and backgrounds. The purpose of this study was to identify how multicultural acceptability affects self-concept and community consciousness by using longitudinal data collected for elementary and middle school students using a latent growth model, and to confirm the relationship between these variables. As a result of the study, first, it was confirmed that the multicultural acceptance of elementary and middle school students influences the development of self-concept and community consciousness. Second, a positive correlation was found between the three variables of multicultural acceptance, self-concept, and community consciousness. This study has implications for establishing educational measures relating to multicultural acceptance, self-concept, and community consciousness for adolescents, who are at the stage where perceptions and attitudes toward diverse races and different cultures are cultivated.

As the number of overseas projects increase, capabilities of managers should be comprehended by handling risks. Therefore, comparison of project managers’ risk perception and risk handling costs from actual cases is necessary to set the management direction. Thus, eleven risk factors that occur frequently in overseas construction were classified into three categories . Perception of 54 international construction managers were collected by survey and ranked by using relative importance index. Consequently, managers perceived that the impact of risks occurring due to the wrong plan was high and conflict risk was low. Then, the data from 20 cases were amplified by applying Monte-Carlo simulation with statistical verification of reliability and normality . Through multivariable regression analysis, the cost impact of the legal conflict risks with the local subcontractors and engineers was the highest,intensely differed with managers’ perception. Specifically, the risks involving various stakeholders with sufficient time to resolve were not recognized, despite the high-cost impact. Though, fully understanding perception of the host-clients or site labors was difficult, this study is vital in that the conceptual gap was narrowed by numerically comparing the difference between risk perception of managers and actual risk cost. , It would be used as a guideline by focusing on factors with high impact for educating managers at overseas sites.

The demand for lithium (Li) has greatly escalated during the past decade and is predicted to increase continuously with the market growth of the electrified transportation and renewable energy, given that Li-ion batteries are the major energy storage method for these sectors. In spite of the urgent need of satisfying the increasing demand of Li, sources of global Li production have been limited in continental brines and pegmatites. In the line with the effort to enhance and diversify the sources of Li supply, this study seeks to predict the production potential of Li from a new source—petroleum source rock brines—and evaluate the most influential factors affecting it. This subject matter is addressed by basin-scale numerical simulation combined with local sensitivity analysis. The numerical simulation with a conceptual model of petroleum source rock system addresses the accumulation of Li in various locations, by taking account for the release of Li from kerogen decomposition reaction in organic-rich source rock, and fate and transport of expelled Li as interacting with reservoir rock. In combination with the numerical simulations, the impacts of various parameters on the Li mass fraction in brines at various observation points are quantified, by conducting local sensitivity analysis. It elucidates the relative sensitivity of Li production potential to the parameters of Li stoichiometry in kerogen decomposition reaction, Na–Li equilibrium coefficient, Na–clay mass fraction in solid phase, Li–clay mass fraction in solid phase, and Na ion mass fraction in brines. Our results provide the conceptual information of most important parameters to be investigated to quantitatively predict the Li production potential from brines at various locations in the petroleum source rock systems that can be used to contribute to the enhancement and diversification of the Li supply.

Background Because premed students do not take courses related to medicine during their first 2 years, they cannot establish their identity as students at medical schools, making it difficult for them to set goals as future doctors. We conducted an early clinical and basic laboratory exposure program for premed students and studied the effects of the program and student satisfaction levels. Methods We performed an early clinical and basic laboratory exposure program for premed students for 2 days and evaluated the effects of the program and student satisfaction with it. The program consisted of two types: type 1, where two to four students formed a group, which was assigned to a particular department to participate and make observations during ward rounds, outpatient clinics, examinations, procedures, and surgeries (in the case of basic laboratory work, the students partook in experimental observations); and type 2, where one student followed a medical school professor to observe the professor’s day. After the program ended, an online survey was conducted to investigate the effects on students, their thoughts, and satisfaction levels. Results In total, 114 students (91.2%) responded to the survey. Approximately 94% of them were satisfied with the program. They found that the program would be useful for deciding on future career paths, gaining knowledge about a department of interest, studying for a medical program after premedical studies, and befriending residents and professors in certain departments. Conclusion Early clinical and basic laboratory exposure programs are recommended for premedical students.

Objective This study investigated the effects of dietary methyl sulfonyl methane (MSM) and selenium (Se) on the laying performance, egg quality, gut health indicators, egg yolk Se content, and antioxidant markers in laying hens. Methods One hundred ninety-two 73-wk-old laying hens were randomly divided into four groups with eight replicates of six hens each. Four diets were prepared in a 2×2 factorial arrangement with or without MSM and Se. The trial lasted for 12 wk. Results There were no interaction effects or main effects (p>0.05) on laying performance and egg quality. However, feed intake increased in Se-fed hens (p = 0.051) and decreased in MSM-fed hens (p = 0.067) compared with that of hens in the control group. Dietary MSM increased (p

Brain type of creatine kinase (CKB) regulates energy homeostasis by reversibly transferring phosphate groups between phosphocreatine and ATP at sites of high energy demand. Several types of cancer cells exhibit upregulated CKB expression, but the function of CKB in cancer cells remains unclear. In this study, we investigated the function of CKB in breast cancer by overexpressing CKB in MDA-MB-231 cells. The overexpression of CKB did not affect cell growth rate, cell cycle distribution, ATP level or key mediators of aerobic glycolysis and lactate dehydrogenase isoform levels. Meanwhile, CKB overexpression did increase resistance to doxorubicin. TGF-β-induced Smad phosphorylation and Smad-dependent transcriptional activity were significantly up-regulated by CKB expression without changes in inhibitory Smad protein levels. Moreover, treatment with TGF-β considerably enhanced cell viability during doxorubicin treatment and decreased doxorubicin-induced apoptosis in CKB-expressing MDA-MB-231 cells compared to control cells. These results suggest that CKB attenuates doxorubicin-induced apoptosis and potentiates resistance to doxorubicin by enhancing TGF-β signaling in MDA-MB-231 cells.

Abstract Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes that reduce COVID-19 host susceptibility is a critical next step. Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX), and perturbagen signatures, we identified IL10RB as the top candidate gene target for COVID-19 host susceptibility. In a series of validation steps, we show that predicted GReX upregulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes and that in vitro IL10RB overexpression is associated with increased viral load and activation of disease-relevant molecular pathways.

Abstract The climate periodically fluctuates on various time scales, however, there remains a lack of consensus on the centennial-scale variabilities and associated driving force. A continuous high-resolution sea surface temperature (SST) record allows for the detection of centennial-scale fluctuations. This study presents a high-resolution SST record covering the last 10,000 years based on the analysis of the alkenone unsaturation index in marine sediment cores off the southwest coast of the Korean Peninsula. Alkenone SST's spectral and wavelet analysis revealed significant periodicities of 414, 190, 135, 102, and 89 years at a > 90% confidence level. These cycles exhibit extreme proximity to the solar activity cycles of 353, 206 (Suess/de Vries cycles), 130, and 104–87 years (Gleissberg cycles), suggesting that the multidecadal to centennial variations in SST are linked to solar forcing. To the best of our knowledge, this is the first high-resolution Holocene SST record that all solar activity cycles on centennial scale match, suggesting centennial-scale variability in the climate system and illustrating the role of solar activity on SST change in the mid-latitude region of the Northern Hemisphere.

Abstract Background Materialism indicates the extent to which an individual’s life is focused on consumerism, or the acquisition of money and possessions. The Material Values Scale (MVS), comprising the factors “success,” “centrality,” and “happiness,” is a well-known rating scale for materialism. However, a Japanese version of the materialism scale has not yet been established, and the details of the factors and effects related to materialism have not yet been clarified in Japan. The purpose of this study is to develop and evaluate the Japanese version of the MVS (J-MVS). Methods We developed the translated J-MVS using a back-translation process. To validate and evaluate the scale based on an online survey, we recruited 500 people, with 100 participants (50 men, 50 women) in five age groups, from 20 to 69 years. We compared and evaluated several factor structure models based on exploratory and confirmatory factor analysis. To evaluate the external criterion-referenced validity of the developed J-MVS scale, we examined the relationship between age, personality, and well-being, which have shown stable relationships with materialism in previous studies. Results We developed two six-item dual-factor models. Both models showed significant positive correlations with social comparison orientation and neuroticism, and had significant negative correlations with various subjective well-being indices, suggesting sufficient external criterion-referenced validity. The J-MVS comprising six positive-worded items (J-MVS-P6; without any reverse-worded items) showed a higher correlation with other indicators than the version comprising six items representing all item types and was considered to have higher external criterion-referenced validity. Conclusions We propose the J-MVS-P6 for use as a materialism scale in Japan. Compared with the findings from other countries, materialism in Japan may be more closely related to subjective well-being. This scale may be used to examine the effectiveness of various intervention methods for improving individuals’ happiness, based on changes in factors closely related to materialism in Japan.

Background/Aims We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Abstract Accurate prediction of postoperative mortality is important for not only successful postoperative patient care but also for information-based shared decision-making with patients and efficient allocation of medical resources. This study aimed to create a machine-learning prediction model for 30-day mortality after a non-cardiac surgery that adapts to the manageable amount of clinical information as input features and is validated against multi-centered rather than single-centered data. Data were collected from 454,404 patients over 18 years of age who underwent non-cardiac surgeries from four independent institutions. We performed a retrospective analysis of the retrieved data. Only 12–18 clinical variables were used for model training. Logistic regression, random forest classifier, extreme gradient boosting (XGBoost), and deep neural network methods were applied to compare the prediction performances. To reduce overfitting and create a robust model, bootstrapping and grid search with tenfold cross-validation were performed. The XGBoost method in Seoul National University Hospital (SNUH) data delivers the best performance in terms of the area under receiver operating characteristic curve (AUROC) (0.9376) and the area under the precision-recall curve (0.1593). The predictive performance was the best when the SNUH model was validated with Ewha Womans University Medical Center data (AUROC, 0.941). Preoperative albumin, prothrombin time, and age were the most important features in the model for each hospital. It is possible to create a robust artificial intelligence prediction model applicable to multiple institutions through a light predictive model using only minimal preoperative information that can be automatically extracted from each hospital.

Abstract This study analyzed the effect of parental supervision of infants at age 4 to 6 months on injuries at age 4 to 12 months. Among all Korean children born during 2008–2009, 464,326 (50.6%) infant had parents who responded to a questionnaire that surveyed their safety and supervision when infant were 4 to 6 months-old. Based on questionnaire score, infant were divided into “safe” or “unsafe” group. 1:1 propensity score matching was used to balance the groups, and injury diagnosis and treatments were analyzed. After matching, we examined the records of 405,862 infant. The unsafe group had significantly increased risk ratios (RRs) for injury of head/neck (RR: 1.06), trunk/abdominopelvic region (RR: 1.12), upper extremities (RR: 1.04), and from burn and frostbite (RR: 1.10). The risks of a wound and fracture and foreign body injury were significantly greater in infant whose parents sometimes left them alone (RR: 1.15 and 1.06, respectively), and whose parents did not always keep their eyes on them (RR: 1.04 and 1.13, respectively). Infant whose parents had a hot drink when carrying them had an increased risk of burn injuries (RR: 1.21). Injuries were less common in infant whose parents provided more supervision.

Abstract Gut dysbiosis is closely associated with the outbreak of inflammatory bowel disease (IBD) and psychiatric disorder. The Enterobacteriaceae population was higher in the feces of patients with inflammatory bowel disease (IBD-F) than in those of healthy control volunteers (HC-F). The Enterococcaceae and Lactobacillaceae populations were higher in the feces of IBD patients with depression (IBD/D+-F) vs. the feces of IBD patients without depression (IBD/D−-F). Therefore, we examined the effects of Klebsiella oxytoca, Escherichia coli, Cronobacter sakazakii, Enterococcus faecium, and Pediococcus acidolactici overpopulated in IBD/D+-F and their byproducts LPS and exopolysaccharide (EPS) on the occurrence of depression and colitis in mice. Oral gavages of Klebsiella oxytoca, Escherichia coli, and Cronobacter sakazakii belonging to Enterobacteriaceae, singly or together, caused dose-dependently colitis and depression-like behaviors in germ-free and specific-pathogen-free mice. Although Enterococcus faecium and Pediococcus acidolactici did not significantly cause colitis and depression-like behaviors, they significantly deteriorated Klebsiella oxytoca- or Escherichia coli-induced colitis, neuroinflammation, and anxiety/depression-like behaviors and increased blood LPS, corticosterone, and IL-6 levels. The EPSs from Enterococcus faecium and Pediococcus acidolactici also worsened Klebsiella oxytoca LPS-induced colitis, neuroinflammation, and depression-like behaviors in mice and increased the translocation of fluorescein isothiocyanate-conjugated LPS into the hippocampus. However, Bifidobacterium longum, which was lower in IBD/D+-F vs. IBD/D−-F, or its EPS suppressed them. In conclusion, Enterococcus faecium and Pediococcus acidolactici, known as a probiotic strain, and their EPSs may be a risk factor for the outbreak of depression and IBD.

Abstract The aminopeptidase activity (AP) of the leukotriene A4 hydrolase (LTA4H) enzyme has emerged as a therapeutic target to modulate host immunity. Initial reports focused on the benefits of augmenting the LTA4H AP activity and clearing its putative pro-inflammatory substrate Pro-Gly-Pro (PGP). However, recent reports have introduced substantial complexity disconnecting the LTA4H modulator 4-methoxydiphenylmethane (4MDM) from PGP as follows: (1) 4MDM inhibits PGP hydrolysis and subsequently inhibition of LTA4H AP activity, and (2) 4MDM activates the same enzyme target in the presence of alternative substrates. Differential modulation of LTA4H by 4MDM was probed in a murine model of acute lung inflammation, which showed that 4MDM modulates the host neutrophilic response independent of clearing PGP. X-ray crystallography showed that 4MDM and PGP bind at the zinc binding pocket and no allosteric binding was observed. We then determined that 4MDM modulation is not dependent on the allosteric binding of the ligand, but on the N-terminal side chain of the peptide. In conclusion, our study revealed that a peptidase therapeutic target can interact with its substrate and ligand in complex biochemical mechanisms. This raises an important consideration when ligands are designed to explain some of the unpredictable outcomes observed in therapeutic discovery targeting LTA4H.

Abstract Background Germ cell mitotic arrest is conserved in many vertebrates, including birds, although the time of entry or exit into quiescence phase differs. Mitotic arrest is essential for the normal differentiation of male germ cells into spermatogonia and accompanies epigenetic reprogramming and meiosis inhibition from embryonic development to post-hatch. However, mitotic arrest was not well studied in chickens because of the difficulty in obtaining pure germ cells from relevant developmental stage. Results We performed single-cell RNA sequencing to investigate transcriptional dynamics of male germ cells during mitotic arrest in DAZL::GFP chickens. Using differentially expressed gene analysis and K-means clustering to analyze cells at different developmental stages (E12, E16, and hatch), we found that metabolic and signaling pathways were regulated, and that the epigenome was reprogrammed during mitotic arrest. In particular, we found that histone H3K9 and H3K14 acetylation (by HDAC2) and DNA demethylation (by DNMT3B and HELLS) led to a transcriptionally permissive chromatin state. Furthermore, we found that global DNA demethylation occurred gradually after the onset of mitotic arrest, indicating that the epigenetic-reprogramming schedule of the chicken genome differs from that of the mammalian genome. DNA hypomethylation persisted after hatching, and methylation was slowly re-established 3 weeks later. Conclusions We found a unique epigenetic-reprogramming schedule of mitotic-arrested chicken prospermatogonia and prolonged hypomethylation after hatching. This will provide a foundation for understanding the process of germ-cell epigenetic regulation in several species for which this process is not clearly described. Our findings on the biological processes related to sex-specific differentiation of prospermatogonia could help studying germline development in vitro more elaborately.

Abstract We investigated the patterns of recurrence and primary endocrine resistance according to estrogen receptor (ER) alpha gene (ESR1) mutations, as assessed by digital droplet (dd) PCR, in patients with non-metastatic ER+ breast cancer. We collected 121 formalin-fixed paraffin-embedded (FFPE) surgical specimens from ER+ breast cancer patients who had relapsed after surgery. Genomic DNA was extracted from the FFPE samples and ESR1 mutations were evaluated using ddPCR. ESR1 mutations were detected in 9 (7.4%) of 121 primary breast cancer specimens. The median recurrence-free interval and overall survival were significantly lower in patients with ESR1 mutations than in those without. Of the patients treated with ET (N = 98), eight had ESR1 mutations. Of these, six (75.0%) had primary endocrine resistance and two (25.0%) had secondary endocrine resistance. By contrast, only 22 of 90 (24.4%) patients without ESR1 mutations had primary endocrine resistance. A multivariable model showed that an ESR1 mutation is a significant risk factor for primary endocrine resistance. Our findings provide clinical evidence that the presence of rare ESR1 mutant clones identified by ddPCR in primary tumors is associated with primary endocrine resistance in an adjuvant setting.

Hemangioblastoma (HB) is a rare benign tumor that most commonly occurs in the cerebellum. HB is composed of neoplastic stromal cells and abundant small vessels. However, the exact origin of stromal cells is controversial. Extraneural HBs have been reported in a small series, and peripheral HBs arising in the adrenal gland are extremely rare. Herein, we report a case of sporadic adrenal HB in a 54-year-old woman. The tumor was a well-circumscribed, yellow mass measuring 4.2 cm in diameter. Histologically, the tumor was composed of small blood vessels and vacuolated stromal cells with clear cytoplasm. On immunohistochemical stain, the stromal cells were positive for S-100 protein, neuron-specific enolase, and synaptophysin. The tumor did not reveal mutation of VHL alleles. We herein present a case of HB of the adrenal gland and review of the literature.

Cerebral small vessel disease (CSVD) includes vascular lesions detected on brain MRI, such as white matter hyperintensities, lacunar infarctions, microbleeds, or enlarged perivascular spaces. There is accumulating evidence that vascular changes may play an important role in development of Alzheimer’s disease (AD), and CSVD lesions detected on brain MRI were reported to be associated with β-amyloid and tau proteins accumulation. As the vascular contribution has therapeutic potential, it is important to understand the association of CSVD with AD and AD biomarkers. This review begins with a brief introduction of AD and AD biomarkers, explains the association between AD and vascular changes, and then details the pathogenesis and MR imaging findings of CSVD. Afterwards, we discuss the association of CSVD with AD and AD biomarkers.

During the coronavirus disease 2019 (COVID-19) pandemic, a novel multisystem inflammatory syndrome in children (MIS-C) has been reported worldwide since the first cases were reported in Europe in April 2020. MIS-C is temporally associated with severe acute respiratory syndrome coronavirus 2 infection and shows Kawasaki disease (KD)-like features. The epidemiological and clinical characteristics in COVID-19, KD, and MIS-C differ, but severe cases of each disease share similar clinical and laboratory findings such as a protracted clinical course, multiorgan involvement, and similar activated biomarkers. These findings suggest that a common control system of the host may act against severe disease insult. To solve the enigmas, we proposed the protein-homeostasis-system hypothesis in that every disease involves etiological substances and the host’s immune system controls them by their size and biochemical properties. Also, it is proposed that the etiological agents of KD and MIS-C might be certain strains in the microbiota of human species and etiological substances in severe COVID-19, KD, and MIS-C originate from pathogen-infected cells. Since disease severity depends on the amounts of inflammation-inducing substances and corresponding immune activation in the early stage of the disease, an early proper dose of corticosteroids and/or intravenous immunoglobulin (IVIG) may help reduce morbidity and possibly mortality among patients with these diseases. Corticosteroids are low cost and an analogue of host-origin cortisol among immune modulators. This study’s findings will help clinicians treating severe COVID-19, KD, and MIS-C, especially in developing countries, where IVIG and biologics supplies are insufficient.

Objectives The outlook of artificial intelligence for healthcare (AI4H) is promising. However, no studies have yet discussed the issues from the perspective of stakeholders in Korea. This research aimed to identify stakeholders’ requirements for AI4H to accelerate the business and research of AI4H. Methods We identified research funding trends from the Korean National Science and Technology Knowledge Information Service (NTIS) from 2015 and 2019 using “healthcare AI” and related keywords. Furthermore, we conducted an online survey with members of the Korean Society of Artificial Intelligence in Medicine to identify experts’ opinions regarding the development of AI4H. Finally, expert interviews were conducted with 13 experts in three areas (hospitals, industry, and academia). Results We found 160 related projects from the NTIS. The major data type was radiology images (59.4%). Dermatology-related diseases received the most funding, followed by pulmonary diseases. Based on the survey responses, radiology images (23.9%) were the most demanding data type. Over half of the solutions were related to diagnosis (33.3%) or prognosis prediction (31%). In the expert interviews, all experts mentioned healthcare data for AI solutions as a major issue. Experts in the industrial field mainly mentioned regulations, practical efficacy evaluation, and data accessibility. Conclusions We identified technology, regulatory, and data issues for practical AI4H applications from the perspectives of stakeholders in hospitals, industry, and academia in Korea. We found issues and requirements, including regulations, data utilization, reimbursement, and human resource development, that should be addressed to promote further research in AI4H.