Microbiomic association between the saliva and salivary stone in patients with sialolithiasis.

Salivary stones, known as sialoliths, form within the salivary ducts due to abnormal salivary composition and cause painful symptoms, for which surgical removal is the primary treatment. This study explored the role of the salivary microbial communities in the formation of sialoliths. We conducted a comparative analysis of microbial communities present in the saliva and salivary stones, and sequenced the 16S rRNA gene in samples obtained from patients with sialoliths and from healthy individuals. Although the diversity in the saliva was high, the essential features of the microbial environment in sialoliths were low diversity and evenness. The association of microbial abundance between stones and saliva revealed a positive correlation between Peptostreptococcus and Porphyromonas, and a negative correlation for Pseudomonas in saliva. The functional potential differences between saliva and stones Bacterial chemotaxis and the citrate cycle were negatively correlated with most genera found in salivary stone samples. However, the functions required for organic compound degradation did not differ between the saliva samples. Although some microbes were shared between the sialoliths and saliva, their compositions differed significantly. Our study presents a novel comparison between salivary stones and salivary microbiomes, suggesting potential preventive strategies against sialolithiasis.

Korean version of the MNREAD acuity chart.

To investigate the efficacy of the Korean version of the Minnesota low vision reading chart. A Korean version consisting of 38 items was prepared based on the MNREAD acuity chart developed by the University of Minnesota. A linguist composed the representative sentences, each containing nine words from second and third grade levels of elementary school. Reading ability was measured for 20-35-year-old subjects with normal visual acuity (corrected visual acuity of logMAR 0.0 or better). The maximum reading speed (words per minute [wpm]) for healthy participants, reading acuity (smallest detectable font size), and critical print size (smallest font size without reduction of reading speed) were analyzed. The average age of the subjects was 28.3 ± 2.6 years (male:female ratio, 4:16). The average reading time for 38 sentences was 3.66 ± 0.69 s, with no differences in the average maximum reading speed between sentences (p = 0.836). The maximum reading speed was 174.2 ± 29.3 and 175.4 ± 27.8 in the right and left eye, respectively. Reading acuity was measured as logMAR 0.0 or better in 80% of the cases. All subjects showed a critical print size of 0.2 logMAR or better. The overall reading ability can be measured using the Korean version of the MNREAD acuity chart, thereby making it useful in measuring the reading ability of those with Korean as their native language.

Neural processing of prototypicality and simplicity of product design in forming design preferences.

The current study investigates the neural correlates when processing prototypicality and simplicity-affecting the preference of product design. Despite its significance, not much is known about how our brain processes these visual qualities of design when forming design preferences. We posit that, although fluency is the perceptual judgment accounting for the positive effects of both prototypicality and simplicity on design preference, the neural substrates for the fluency judgment associated with prototypicality would differ from those associated with simplicity. To investigate these issues, we conducted an fMRI study of preference decisions for actual product designs with different levels of prototypicality and simplicity. The results show a significant functional gradient between the preference processing of simplicity and prototypicality-i.e., involvement of the early ventral stream of visual information processing for simplicity evaluation but recruitment of the late ventral stream and parietal-frontal brain regions for prototypicality evaluation. The interaction between the simplicity and prototypicality evaluations was found in the extrastriate cortex in the right hemisphere. The segregated brain involvements suggest that the fluency judgment for prototypicality and simplicity contribute to preference choice in different levels of cognitive hierarchy in the perceptual mechanism of the design preference.

Deep learning-based detection and quantification of brain metastases on black-blood imaging can provide treatment suggestions: a clinical cohort study.

OBJECTIVES: We aimed to evaluate whether deep learning-based detection and quantification of brain metastasis (BM) may suggest treatment options for patients with BMs. METHODS: The deep learning system (DLS) for detection and quantification of BM was developed in 193 patients and applied to 112 patients that were newly detected on black-blood contrast-enhanced T1-weighted imaging. Patients were assigned to one of 3 treatment suggestion groups according to the European Association of Neuro-Oncology (EANO)-European Society for Medical Oncology (ESMO) recommendations using number and volume of the BMs detected by the DLS: short-term imaging follow-up without treatment (group A), surgery or stereotactic radiosurgery (limited BM, group B), or whole-brain radiotherapy or systemic chemotherapy (extensive BM, group C). The concordance between the DLS-based groups and clinical decisions was analyzed with or without consideration of targeted agents. The performance of distinguishing high-risk (B + C) was calculated. RESULTS: Among 112 patients (mean age 64.3 years, 63 men), group C had the largest number and volume of BM, followed by group B (4.4 and 851.6 mm3) and A (1.5 and 15.5 mm3). The DLS-based groups were concordant with the actual clinical decisions, with an accuracy of 76.8% (86 of 112). Modified accuracy considering targeted agents was 81.3% (91 of 112). The DLS showed 95% (82/86) sensitivity and 81% (21/26) specificity for distinguishing the high risk. CONCLUSION: DLS-based detection and quantification of BM have the potential to be helpful in the determination of treatment options for both low- and high-risk groups of limited and extensive BMs. CLINICAL RELEVANCE STATEMENT: For patients with newly diagnosed brain metastasis, deep learning-based detection and quantification may be used in clinical settings where prompt and accurate treatment decisions are required, which can lead to better patient outcomes. KEY POINTS: • Deep learning-based brain metastasis detection and quantification showed excellent agreement with ground-truth classifications. • By setting an algorithm to suggest treatment based on the number and volume of brain metastases detected by the deep learning system, the concordance was 81.3%. • When dividing patients into low- and high-risk groups, the sensitivity for detecting the latter was 95%.

The association of tonsillar microbiota with biochemical indices based on obesity and tonsillar hypertrophy in children.

The correlation between tonsil microbiome and tonsillar hypertrophy has not been well established. Given that oral dysbiosis is related to several metabolic diseases and that tonsillar hypertrophy leads to disordered breathing during sleep and obesity in children, it is necessary to investigate the relationship between the oral microbiome and tonsillar hypertrophy. After 16S rRNA amplicon sequencing of tonsillectomy samples, we evaluated the correlation between the tonsil microbiome and biochemical blood indices in pediatric patients who underwent tonsillectomy. Groups are classified into two categories: based on BMI, and grades 2, 3, and 4 based on tonsil size. Children with obesity and tonsillar hypertrophy have similar microbiome compositions and induce comparable changes in microbiome abundance and composition, confirming the association from a metagenomic perspective. In addition, obesity and tonsillar hypertrophy demonstrated a strong correlation with the Proteobacteria to Firmicutes (P/F) ratio, and among various biochemical indicators, alanine aminotransferase (ALT) levels increase with obesity and tonsillar hypertrophy, indicating a possible association of tonsil microbiome and liver metabolism. These novel findings demonstrate the significance of the tonsil microbiome and suggest the need for tonsil regulation, particularly during childhood.

Association between maternal coronavirus disease 2019 and transient tachypnea of the newborn: a single-center study.

BACKGROUND: Limited clinical reports have investigated the effects of maternal coronavirus disease 2019 (COVID-19) on fetuses and neonates. PURPOSE: This retrospective study aimed to assess the impact of maternal COVID-19 on neonates during the perinatal period, including neonatal clinical outcomes, versus the outcomes of neonates of mothers without COVID-19. METHODS: Neonates born to COVID-19-infected mothers at the National Health Insurance Service Ilsan Hospital between February 2021 and March 2022 were included. Those with gestational age (GA) ≥35+0 weeks who were born within 2 weeks of the maternal infection were matched 1:2 with a control group based on GA. The main outcomes were respiratory diseases, including transient tachypnea of the newborn (TTN), respiratory distress syndrome, meconium aspiration syndrome, the need for respiratory support, and length of hospital stay. Uni- and multivariate logistic regression analyses were performed and adjusted for relevant covariates, including maternal age, obstetric complications (hypertension and gestational diabetes), delivery mode, birth weight, sex, and small-for-gestational-age status. RESULTS: The case group comprised 103 neonates (mean GA, 38.5±1.3 weeks; mean birth weight, 3,121±397 g), while the control group included 206 neonates (mean GA, 38.4±1.2 weeks; mean birth weight, 3088±428 g). In the case and control groups, the proportion of cesarean sections was 91% and 40%, respectively, while the proportion of male infants was 56% and 47%, respectively. After adjusting for covariates, the case group had a higher risk of TTN (adjusted odd ratio [AOR], 3.69; 95% confidence interval [CI], 1.69-8.07), noninvasive respiratory ventilator use (AOR, 2.28; 95% CI, 1.05-4.97), and oxygen support (AOR, 4.83; 95% CI, 1.46-15.95). CONCLUSION: Newborns born to COVID-19-infected mothers are at increased risk of TTN and may require respiratory support. Close monitoring of respiratory symptoms is crucial in neonates.

Nitrosylation of ß2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice.

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of ß2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-ß2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-ß2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION: This is the first discovery of a new target molecule of NO, ß2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-ß2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Therapeutic Effect of HDAC5 Binding and Cell Penetrating Peptide for the Treatment of Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is an incurable disease that negatively influences the quality of life of patients. Current and emerging therapies target proinflammatory cytokines and/or receptors to downregulate proinflammatory responses, but insufficient remission requires other therapeutic agents. Herein, we report that the synthetic anti-inflammatory peptide 15 (SAP15) is capable of cell penetration and anti-inflammatory activity in human macrophages. METHODS: SAP15 was labeled with fluorescence and administered to human leukemia monocytic cells (THP-1) cells for cell penetration analysis. Using biolayer interferometry analysis, the binding affinity of SAP15 with histone deacetylase 5 (HDAC5) was measured. SAP15-treated THP-1 cells were analyzed by protein phosphorylation assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In addition, in vivo analysis of the therapeutic effect on IBD was observed in a dextran sulfate sodium (DSS)-induced model. Samples from SAP15-treated mice were analyzed at both the macroscopic and microscopic levels using ELISA, myeloperoxidase (MPO) assays, and histological evaluations. RESULTS: SAP15 was internalized within the cytosol and nucleus of THP-1 cells and bound to the HDAC5 protein. SAP15-treated macrophages were assessed for protein phosphorylation and showed inhibited phosphorylation of HDAC5 and other immune-related proteins, which led to increased M2-like macrophage markers and decreased M1-like macrophage markers and tumor necrosis factor-α and interleukin-6 cytokine levels. The SAP15 treatment on IBD model showed significant recovery of colon length. Further histological analysis of colon demonstrated the therapeutic effect of SAP15 on mucosal layer. Moreover, proinflammatory cytokine levels and MPO activity from the plasma show that SAP15 is effective in reduced proinflammatory responses. CONCLUSION: These findings suggest that SAP15 is a novel peptide with a novel cell-penetrating peptide with anti-inflammatory property that can be used as a therapeutic agent for IBD and other inflammatory diseases.

Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population.

Hundreds of genetic variants for body mass index (BMI) have been identified from numerous genome-wide association studies (GWAS) in different ethnicities. In this study, we aimed to develop a polygenic risk score (PRS) for BMI for predicting susceptibility to obesity and related traits in the Korean population. For this purpose, we obtained base data resulting from a GWAS on BMI using 57,110 HEXA study subjects from the Korean Genome and Epidemiology Study (KoGES). Subsequently, we calculated PRSs in 13,504 target subjects from the KARE and CAVAS studies of KoGES using the PRSice-2 software. The best-fit PRS for BMI (PRSBMI) comprising 53,341 SNPs was selected at a p-value threshold of 0.064, at which the model fit had the greatest R2 score. The PRSBMI was tested for its association with obesity-related quantitative traits and diseases in the target dataset. Linear regression analyses demonstrated significant associations of PRSBMI with BMI, blood pressure, and lipid traits. Logistic regression analyses revealed significant associations of PRSBMI with obesity, hypertension, and hypo-HDL cholesterolemia. We observed about 2-fold, 1.1-fold, and 1.2-fold risk for obesity, hypertension, and hypo-HDL cholesterolemia, respectively, in the highest-risk group in comparison to the lowest-risk group of PRSBMI in the test population. We further detected approximately 26.0%, 2.8%, and 3.9% differences in prevalence between the highest and lowest risk groups for obesity, hypertension, and hypo-HDL cholesterolemia, respectively. To predict the incidence of obesity and related diseases, we applied PRSBMI to the 16-year follow-up data of the KARE study. Kaplan-Meier survival analysis showed that the higher the PRSBMI, the higher the incidence of dyslipidemia and hypo-HDL cholesterolemia. Taken together, this study demonstrated that a PRS developed for BMI may be a valuable indicator to assess the risk of obesity and related diseases in the Korean population.

Genetic association study identifies genetic variants for non-alcoholic fatty liver without comorbidities in the Korean population.

BACKGROUND: Non-alcoholic fatty liver (NAFL) refers to a disease in which fat builds up in the liver, similar to what occurs for those who drink a lot of alcohol, even in cases of not drinking alcohol at all or only in a small amount. Along with non-alcoholic steatohepatitis (NASH), NAFL is a type of non-alcoholic fatty liver disease (NAFLD). Currently, the prevalence of NAFLD is increasing worldwide. A wide range of comorbidities that can increase the risk of NAFLD includes obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. OBJECTIVE: This study aimed to discover genetic variants for NAFL in the Korean population. METHODS: Differing from previous studies, we conducted a genome-wide association study for NAFL in the selected subjects without comorbidities to rule out bias due to the inclusion of confounding effects of comorbidities. We grouped 424 NAFL cases and 5,402 controls from the Korean Genome and Epidemiology Study (KoGES) subjects without comorbidities such as dyslipidemia, type 2 diabetes, and metabolic syndrome. All subjects including cases and controls did not consume alcohol at all, or consumed less than 20 g/day for men and less than 10 g/day for women. RESULTS: The logistic association analysis adjusting for sex, age, BMI, and waist circumference identified one novel genome-wide significant variant (rs7996045, P = 2.3 × 10-8) for NAFL. This variant was located in the intron of CLDN10 and was not detected using previous conventional approaches in which confounding effects resulting from comorbidities were not considered in the study design stage. In addition, we detected several genetic variants showing suggestive association for NAFL (P < 10-5). CONCLUSION: The unique strategy in our association analysis of excluding major confounding factors provides, for the first time, an insight into the genuine genetic basis influencing NAFL.

Real-Time Prediction for Neonatal Endotracheal Intubation Using Multimodal Transformer Network.

Neonates admitted to neonatal intensive care units (NICUs) are at risk for respiratory decompensation and may require endotracheal intubation. Delayed intubation is associated with increased morbidity and mortality, particularly in urgent unplanned intubation. By accurately predicting the need for intubation in real-time, additional time can be made available for preparation, thereby increasing the safety margins by avoiding high-risk late intubation. In this study, the probability of intubation in neonatal patients with respiratory problems was predicted using a deep neural network. A multimodal transformer model was developed to simultaneously analyze time-series data (1-3 h of vital signs and Fi[Formula: see text] setting value) and numeric data including initial clinical information. Over a dataset including information of 128 neonatal patients who underwent noninvasive ventilation, the proposed model successfully predicted the need for intubation 3 h in advance (area under the receiver operator characteristic curve = 0.880 ± 0.051, F1-score = 0.864 ± 0.031, sensitivity = 0.886 ± 0.041, specificity = 0.849 ± 0.035, and accuracy = 0.857 ± 0.032). Moreover, the proposed model showed high generalization ability by achieving AUROC 0.890, F1-score 0.893, specificity 0.871, sensitivity 0.745, and accuracy 0.864 with an additional 91 dataset for testing.

Predicting the need for intubation within 3 h in the neonatal intensive care unit using a multimodal deep neural network.

Respiratory distress is a common chief complaint in neonates admitted to the neonatal intensive care unit. Despite the increasing use of non-invasive ventilation in neonates with respiratory difficulty, some of them require advanced airway support. Delayed intubation is associated with increased morbidity, particularly in urgent unplanned cases. Early and accurate prediction of the need for intubation may provide more time for preparation and increase safety margins by avoiding the late intubation at high-risk infants. This study aimed to predict the need for intubation within 3 h in neonates initially managed with non-invasive ventilation for respiratory distress during the first 48 h of life using a multimodal deep neural network. We developed a multimodal deep neural network model to simultaneously analyze four time-series data collected at 1-h intervals and 19 variables including demographic, physiological and laboratory parameters. Evaluating the dataset of 128 neonates with respiratory distress who underwent non-invasive ventilation, our model achieved an area under the curve of 0.917, sensitivity of 85.2%, and specificity of 89.2%. These findings demonstrate promising results for the multimodal model in predicting neonatal intubation within 3 h.

Topical Delivery of Cell-Penetrating Peptide-Modified Human Growth Hormone for Enhanced Wound Healing.

Protein drugs have been emerging as a class of promising therapeutics. However, their topical application has been limited by their high molecular weight and poor permeability to the cell membrane. In this study, we aimed to enhance human growth hormone (hGH) permeability for topical application by conjugation of TAT peptide, a cell-penetrating peptide, to hGH via crosslinker. After TAT was conjugated to hGH, TAT-hGH was purified by affinity chromatography. TAT-hGH significantly increased cell proliferation compared with the control. Interestingly, the effect of TAT-hGH was higher than hGH at the same concentration. Furthermore, the conjugation of TAT to hGH enhanced the permeability of TAT-hGH across the cell membrane without affecting its biological activity in vitro. In vivo, the topical application of TAT-hGH into scar tissue markedly accelerated wound healing. Histological results showed that TAT-hGH dramatically promoted the re-epithelialization of wounds in the initial stage. These results demonstrate TAT-hGH as a new therapeutic potential drug for wound healing treatment. This study also provides a new method for topical protein application via enhancement of their permeability.

Biocompatible 7-nitro-2,1,3-benzoxadiazole-embedded naphthalimide for exploring endogenous H2S in living cells.

Hydrogen sulfide (H2S) is a central signaling and antioxidant biomolecule involved in various biological processes. As inappropriate levels of H2S in the human body are closely related to various diseases, including cancer, a tool capable of detecting H2S with high selectivity and sensitivity in living systems is urgently required. In this work, we intended to develop a biocompatible and activatable fluorescent molecular probe for detecting H2S generation in living cells. The 7-nitro-2,1,3-benzoxadiazole-imbedded naphthalimide (1) probe presented here responds specifically to H2S and produces readily detectable fluorescence at 530 nm. Interestingly, probe 1 exhibited significant fluorescence responses to changes in endogenous H2S levels as well as high biocompatibility and permeability in living HeLa cells. This allowed for the real-time monitoring of endogenous H2S generation as an antioxidant defense response in the oxidatively stressed cells.

Distinction of Male and Female Trees of Ginkgo biloba Using LAMP.

Ginkgo biloba is utilized as food, medicine, wood, and street trees among other things. The objective of this study was to develop a loop-mediated isothermal amplification (LAMP) assay for gender distinction of G. biloba. Male-specific SCAR gene can be utilized to identify G. biloba gender using LAMP. The optimized LAMP conditions, temperature 60 °C, 2-mM MgSO4, and [F3/B3]:[FIP/BIP] primer ratio of 1:4 were selected as final conditions. The G. biloba SCAR LAMP displayed a sensitivity of 10 ng when amplified by concentration under the optimum conditions. Additionally, it demonstrated a particular response in male with SYBR Green I in LAMP analysis that can be a more powerful tool for field and scale-up applications. Our work represents a first attempt to identify G. biloba gender using LAMP and offers an efficient and reliable tool for roadside landscaping.

Development of Pavement Material Using Crumb Rubber Modifier and Graphite Nanoplatelet for Pellet Asphalt Production.

The purpose of this research was to promote the recycling of pellet asphalt with Crumb Rubber Modifier (CRM) and Graphite Nanoplatelet (GNP) in pothole restoration. In this study, several laboratory tests were carried out on mixes containing CRM content ratios of 5%, 10%, and 20% and GNP content of 3% and 6% in order to identify the ideal mixing ratio of pellet-type asphalt paving materials. The Marshall stability test, the Hamburg wheel tracking test, and the dynamic modulus test were all performed to compare the effectiveness of the proposed method and heated asphalt combinations. Afterward, the full-scale testbed was conducted to verify the practical application between the proposed method and popular pothole-repairing materials. Both laboratory and field test findings confirmed that the asphalt pavement using 5% CRM and 6% GNP improved the resistance to plastic deformation and anti-stripping compared to the generally heated asphalt paving material, thereby extending road life. However, the resistance to fatigue cracking can be slightly reduced by incorporating these additives. Overall, the CRM and GNP asphalt pellet approach is a feasible solution for sustainable pavement maintenance and rehabilitation, particularly in small-scale damage areas such as potholes.

Impact of time to full enteral feeding on long-term neurodevelopment without mediating by postnatal growth failure in very-low-birth-weight-infants.

This study aimed to determine if time to achieve full enteral feeding (TFF) directly impacted long-term neurodevelopmental delay (NDD) and whether long-term postnatal growth failure (PGF) was a mediator of this association in very-low-birth-weight (VLBW) infants. Using prospectively collected cohort data from the Korean Neonatal Network, we included eligible VLBW infants who achieved TFF at least once and classified enrolled infants into four groups using exposure severity (P1 to P4 as TFF < 16, 16-30, 31-45, and > 45 postnatal days, respectively). After adjusting for confounding variables, survival without NDD was significantly decreased in P4 infants compared with that in P2 infants. P1 infants had a lower risk of weight and height PGF than P2 infants; however, P4 infants had higher risks of height and head circumference PGF than P2 infants. Weight and height PGF were significantly associated with an increased risk of NDD. In mediation analysis, early and delayed TFF revealed direct positive and negative impacts, respectively, on the risk of NDD without mediation by PGF. TFF impacted survival without NDD, and PGF did not mediate this association in VLBW infants. Additionally, these results can be translated into evidence-based quality improvement practice.

Vacuoles isolated from Saccharomyces cerevisiae inhibit differentiation of 3T3-L1 adipocyte.

Yeast vacuoles contain various hydrolytic enzymes including lipase. They play important roles in intracellular signaling and metabolism. Using these characteristics, the aim of this study is to determine effects of yeast vacuoles on the triglyceride accumulation and differentiation of pre-adipocytes to adipocytes using 3T3-L1 cells. The accumulation of lipid droplets and triglyceride were reduced after treatment with vacuoles. As a result of not maintaining the expression of C/EBPß and C/EBPδ in vacuole-treated adipocytes, expression levels of C/EBPα and PPARγ in vacuole-treated adipocytes were significantly reduced. The expression of adiponectin in the late differentiation stage was increased compared to that in the control. By confirming that vacuolar enzymes also inhibit differentiation of adipocytes same as vacuoles, it can be concluded that the adipogenesis inhibitory effect of vacuoles is by lipase of vacuolar enzymes. Yeast-derived vacuoles could be an important source for inhibiting accumulation of lipids and obesity-related inflammation by suppressing adipogenesis.

Long-term outcomes of preterm infants in the first 6 years of life: a nationwide population-based study in Korea.

This study examined the relationship between gestational age and long-term outcomes up to 6 years of age using population-based big data from the National Health Insurance Service in Korea. This retrospective observational cohort study used data from the National Health Information Database (2011-2017). All children born in Korea during 2011 (January 1-December 31) were eligible and were followed up until 2017. Gestational age groups were divided into extremely preterm (< 28 weeks), very preterm (28-31 weeks), moderate-to-late preterm (32-36 weeks), and full-term (37-41 weeks). The survival rate, neurodevelopmental diseases, hearing or visual impairment, and respiratory morbidities were compared for each gestational age group. In total, 370,301 children were included in the analysis. The total survival rate increased with increasing gestational age. Furthermore, the risk of neurodevelopmental diseases (i.e., epilepsy, cerebral palsy, delayed development, mental retardation, language disorder, developmental coordination disorder, autism spectrum disorder), hearing or visual impairment, and asthma-related inhaler prescription increased with decreasing gestational age, despite adjustment for covariates. CONCLUSION: Lower gestational age was associated with an increase in a wide spectrum of adverse neurodevelopmental and respiratory outcomes in the first 6 years of life. Although morbidities were highest at the earliest gestational ages, moderate-to-late preterm children were significantly associated with increased adverse outcomes compared with full-term children. Our findings prove this under-recognized group's long-term follow-up and policy support. WHAT IS KNOWN: • Infants born preterm are at high risk for neurodevelopmental and various medical health problems. • Nationwide research on long-term outcomes for moderate-to-late preterm birth is sparse. WHAT IS NEW: • In this nationwide cohort study, lower gestational age at birth was inversely associated with increased adverse neurodevelopmental and respiratory outcomes in the first 6 years of life. • Long-term follow-up and policy support are required for moderate-to-late preterm children who are at risk of increased adverse outcomes compared with full-term births.