Intellectual disability (ID) is characterized by deficits in cognition and adaptive behavior, with few treatment options. Tumor Suppressor Candidate 3 (TUSC3) has been genetically linked to autosomal recessive ID, but its molecular mechanism and therapeutic potential remain unclear. Here we show that TUSC3 is essential for endoplasmic reticulum (ER) Mg²⁺ homeostasis and neuronal function. Using a TUSC3 knockout (KO) mouse model, we find ID-like phenotypes including impairments in learning, memory, stress adaptation, and social behavior. Mechanistically, TUSC3 forms an ER-localized Mg²⁺ transport complex with ERMA and its loss leads to ER Mg²⁺ depletion, PERK-eIF2α pathway activation, synaptic dysfunction, and neuronal vulnerability. Fibroblasts from TUSC3 mutant patients similarly exhibit ER Mg²⁺ deficiency and heightened ER stress. Magnesium supplementation restores ER Mg²⁺ levels, reduces ER stress, and rescues cognitive deficits. Our findings establish ER Mg²⁺ dysregulation as a key driver of neurodevelopmental dysfunction and a promising therapeutic target.

Hair loss, also known as androgenetic alopecia, leads to the progressive miniaturization of hair follicles and a reduction in the number of hair follicles in the anagen phase. While there are chemical products used to treat hair loss, their side effects have recently emerged. Therefore, in this study, we investigated natural products that alleviate hair loss. Ganoderma Lucidum (G. Lucidum), a traditional oriental medicine, has been extensively studied for its effects on antioxidants, regeneration, and anti-inflammation. In this study, we analyzed G. Lucidum and Ganoderic acid A (GAA), the most abundant triterpenoid in G. Lucidum, to evaluate hair loss prevention in vitro, ex vivo, and clinical tests. We found that G. Lucidum extract and GAA both improved the proliferation of human dermal papilla cells (hDPCs) and human hair germinal matrix cells (HHGMCs). Also, G. Lucidum extract and GAA increased the expression of growth factors, such as VEGF and IGF-1 in each hair cell. In addition, G. Lucidum extract and GAA showed hair follicle growth in length and diameter, compared to the control (vehicle) group in an ex vivo human scalp-derived hair follicle culture model. Moreover, they both suppressed the progression to the catagen phase of the hair growth cycle. Furthermore, clinical trials (24-week, randomized, double-blind, controlled) demonstrate that G. Lucidum extract and GAA applied to shampoo (leave off) and tonic (leave on) formulations have significant hair loss inhibition effects. Collectively, these results indicate that G. Lucidumextract and its active component, GAA, alleviate and delay the progression of alopecia, and they could be used as an effective therapeutic for the treatment of hair loss.

The aim of this study was to propose a prediction model based on machine learning algorithms for spontaneous preterm delivery (sPTD) prediction in singleton pregnancies using the cervical elastographic markers obtained at mid-trimester. Multicentre prospective study was performed between June 2018 to December 2020 by the Korean Research Group of Cervical Elastography (grant ID: HI18C1696). Women with singleton pregnancies who underwent ultrasound between 18+0 and 24+0 weeks of gestation were eligible for analysis. Cervical elastography were performed using E-cervixTM (WS80A and HERA, Samsung Medison). sPTD was defined as delivery < 37 weeks of gestation due to either spontaneous preterm labour or rupture of membranes. The final data set included data from 1,518 patients and this data set was split into training and validation data sets. Three machine learning classification algorithms (Lasso regression, random forest and XGBoost) were used to build sPTD prediction models. Model performance in predicting sPTD from elastographic data and clinical factors was assessed using validation data set. Among 1,518 patients, 78 (5.1%) had spontaneous preterm delivery. The mean area under the receiver operating characteristic curve (AUC) for Lasso regression, random forest, and Xgboost model were 0.695, 0.704 and 0.723, respectively. The sPTD prediction score based on Xgboost was developed based on 9 selected variables: cervix length at examination, maternal age, maternal weight, internal os strain (IOS), external os strain (EOS), IOS to EOS ratio, elasticity contrast index, hardness ratio 30. The prediction model had an AUC of 0.737, significantly higher than CL alone (AUC = 0.594). The prediction model using mid-trimester cervical elastographic parameters had a potential value in predicting spontaneous preterm birth in single pregnancies.

Most of the previous studies have established the association between Doppler indices and fetal growth restriction (FGR), with a primary focus on umbilical artery (UA), and middle cerebral artery (MCA). This study aims to assess changes in ultrasonographic uteroplacental-fetal biometry and Doppler measurements more comprehensively including umbilical vein (UV) flow, placental and uterine wall thickness between fetuses with and without FGR. This multicentre observational study will be conducted as both retrospective and prospectively. We will enrol singleton pregnant women who have underwent at least one fetal ultrasound scan during the routine antepartum care. Women with fetuses that have chromosomal or structural abnormalities will be excluded. The study will measure U-AID indices, which are including uterine artery, UA, MCA, and UV flow, as well as placental and uterine wall thickness, and estimated fetal body weight during each trimester. The study population will be divided into two groups based on fetal growth, which are the FGR group and the control group. We will compare the U-AID indices between the two groups and evaluate the association between these indices and adverse perinatal outcomes in the FGR group. Additionally, we will develop a predictive model for adverse perinatal outcomes in the FGR group using both clinical risk factors and U-AID indices by multivariable logistic regression analysis. Not applicable. The U-AID study provides a comprehensive evaluation of uteroplacental-fetal biometry and Doppler indices according to fetal growth. This study will provide valuable insights into the potential utility of these indices in predicting and managing adverse perinatal outcomes. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Pregnancies complicated with fetal growth restriction (FGR) have increased risk of short- and long-term neonatal morbidities. To determine altered Doppler ultrasound findings that are associated with composite adverse perinatal outcome (CAPO) of early- and late-onset FGR with estimated fetal weight (EFW) < 3rd centile. A multicentre retrospective study was conducted on women with FGR of EFW < 3rd centile by Hadlock standard. Ultrasound findings were obtained typically by one week before birth. As Doppler indices change with gestational age, values were expressed into z-scores. CAPO was defined as the occurrence of at least two of 5-min Apgar score < 7, umbilical artery (UA) pH < 7.10, neonatal care unit (NICU) admission, respiratory distress, neonatal enterocolitis, intraventricular hemorrhage, sepsis, perinatal loss, and emergency Caesarean section for fetal distress. Logistic regression analysis was used to determine the association between Doppler ultrasound variables and CAPO. In early onset, 114 singleton pregnancies were included. On multivariable logistic regression analysis, z-score of cerebroplacental ratios (CPR) (p = 0.021) was associated independently with CAPO. Z-score of UA pulsatility index (PI) and middle cerebral artery (MCA) PI were not significant. In late onset, 86 singleton pregnancies were included. Z-score of MCA PI (p = 0.021) and of CPR (p = 0.008) were associated independently with CAPO. When compared between groups with CPR < 5th centile and those without. In the group with CPR < 5th centile, emergency Caesarean section for fetal distress was significantly high and UA pH was low at early-onset FGR. In late-onset FGR, low UA pH, stay in NICU, and pre-eclampsia in pregnancy were increased. In FGR of EFW < 3rd centile, z-score of CPR is associated independently with CAPO in early-onset FGR. Along with z-score of CPR, z-score of MCA PI is also associated independently with CAPO in late-onset FGR.

Objectives: MicroRNAs (miRNA) are regulators of cellular processes including (anti-) angiogenesis and differentiation of trophoblast cells.They play a role in the pathophysiology of pre-eclampsia (PE).The aim of this study is to investigate the

To develop a prediction model for estimating risk of imminent spontaneous preterm delivery (sPTD) using cervical elastography among women with short cervical length (CL) (≤25 mm). This prospective study was conducted by the Korean Research Group of Cervical Elastography (grant ID: HI18C1696). Women with short CL between 16 and 32 weeks of gestation were enrolled from June 2018 to December 2020 from 7 institutions. Cervical elastography using E-Cervix™ (WS80A, Samsung Medison, Seoul, Korea) was performed according to the standardised protocol previously suggested. Elastographic parameters were compared between term delivery group and preterm delivery (PTD) group. By the analysis of multivariable logistic regression and Cox proportional hazard model (Cox PH model), covariates were selected. On the basis of the predictive model with the identified risk factors a nomogram was constructed for predicting probability of sPTD and of being undelivered within 14- and 28-days. The accuracy of predicting model was evaluated using receiver operating characteristic curve analysis calculating the area under the curve (AUC) and external validation was performed. A total of 334 women were included. The prevalence of sPTD was 24.3% (81/334) and median gestational age at examination (GAE) was 24.6 weeks (16.1-32.0). The multivariable logistic regression and multivariable Cox PH model selected six independent predictors of sPTD through hierarchical modelling: twin pregnancy, GAE, CL, funnelling, IOS strain and mean strain. By adding the scores assigned on the points scale for each variable, the nomogram might determine the probability of sPTD and of pregnancy maintenance. The AUC of selected model to predict sPTD was 0.7658 and the AUC of delivery-free probability at 14- and 28-days after exam were 0.7770 and 0.8056. With external validation, the AUC of nomogram to predict sPTD was 0.6319. We confirmed that cervical elastography is a useful adjunctive tool to predict sPTD in women with short CL.

The traditional fetal growth restriction is defined as an estimated fetal weight (EFW) or abdominal circumference < 10th percentile for gestational age and associated with adverse perinatal outcomes. Sometimes, fetuses with 10-15th percentile of EFW have a similar prognosis and outcomes as traditional FGR fetuses. So, we compare Doppler findings and perinatal outcomes in fetuses according to EFW near 10th percentile. (3-10th vs. 10-15th percentile). This multicentre study included fetuses, whose EFW was under 15th and above 3rd percentile. All recruited fetuses underwent sonographic assessment of fetal weight and Doppler studies before birth. We evaluated Doppler findings and perinatal outcomes of early- and late-onset FGR, separately, according to EFW percentile (3rd-10th percentile vs. 10th-15th percentile). Total 348 fetuses with EFW around 10th percentile were included. In early-onset FGR, EFW of 59 fetuses was under 10th and above 3rd percentile (Group A) and that of 17 fetuses was under 15th and above 10th percentile (Group B). Systolic/diastolic ratio of umbilical artery was higher in group A than in group B (3.0 vs. 2.5, p = 0.011). However, percentiles of UA-PI, MCA-PI and CPR were not significantly different between two groups. Neonatal outcomes except NICU hospitalisation were not significantly different between two groups. In late-onset FGR, EFW percentile of 176 fetuses was under in group A and that of 96 fetuses was in group B. Doppler findings were not different. The rate of NICU admission was higher and mean duration of NICU hospitalisation was longer in group A than in group B. However, other neonatal outcomes were not significantly different, like early-onset FGR. In both early- and late-onset FGR, there is no difference in Doppler findings around 10th percentile of EFW. Although, the rate of NICU admission was high in group A than in the group B, there is no difference in other neonatal outcomes.

To evaluate whether the right modified myocardial performance index (Mod-RMPI) can predict adverse perinatal outcomes in pregnancies complicated with fetal growth restriction (FGR). We conducted a multicentre prospective study including 57 singleton pregnant women at 24-38 weeks of gestation complicated with FGR [estimated fetal weight (EFW) < 10th centile and 59 controls. We measured the Mod-RMPI by using MPI+ on HERA W10 (Samsung Medison Co. Ltd., Seoul, Republic of Korea) three times at every 191 examinations. We defined adverse perinatal outcomes as iatrogenic preterm delivery before 37 weeks, a birthweight < 2000g, 5-min Apgar < 7 or umbilical arterial pH < 7.200. We compared Mod-RMPI between FGR and control groups as well as evaluated whether there was a difference in Mod-RMPI according to the occurrence of perinatal outcomes in the FGR group. Although Mod-RMPI results were similar at initial examination [0.527 (0.368-0.677) vs. 0.555 (0.367-0.771), p = 0.066], there was a significant difference in the whole of Mod-RMPI results between two groups [0.520 (0.368-0.710) vs. 0.555 (0.367-0.781), p = 0.009]. There were 27 adverse perinatal outcomes among 93 deliveries. Interestingly, when we evaluated total tests, the median Mod-RMPI was higher in the adverse perinatal outcome group [0.527 (0.367-0.750) vs. 0.555 (0.377-0.781), p = 0.039]. Also, there were nine cases of adverse perinatal outcomes with normal umbilical artery Doppler (10/69,12.7%). Notably, we found that the Mod-RMPI result of these pregnancies were higher compared to normal perinatal outcomes [0.533 (0.367-0750) vs. 0.607 (0.437-0.781), p = 0.001]. Our data suggest the changes of Mod-RMPI could be preceded to umbilical artery Doppler deterioration. It could be used an ancillary tool to conventional fetal surveillance in the management of FGR pregnancies.

To assess the modified myocardial performance index (Mod-MPI) of fetal left and right heart in pregnant women with diabetes mellitus and compare it with the Mod-MPI in the control group. This was a multicentre prospective cross-sectional study to assess the Mod-MPI of the fetal heart for singleton pregnant women with diabetes mellitus in the third trimester. Mod-MPI was measured using an automated measurement system for the left heart and a semi-automated system for the right fetal heart (MPI+, Samsung Medison, Seoul, Republic of Korea). Singleton pregnant women with pregestational diabetes or gestational diabetes beyond 28 weeks of gestation were included in the diabetes group, and uncomplicated pregnant women were included in the control group. A total of 120 measurements (67 diabetes, 53 controls) were included in this study. The mean gestational age of measurement was 32.7 ± 2.4 weeks in the control group and 34.1 ± 3.4 weeks in the diabetes group. There was no significant difference for Mod-MPI of the left fetal heart between the diabetes and the control group (0.52 [0.47-0.57] vs. 0.50 [0.45-0.53], p = 0.067). Mod-MPI of the right heart was significantly higher in the diabetes group (0.57 [0.50-0.62]) compared to the control group (0.52 [0.47-0.57], p = 0.0070). However, there was no significant difference in Mod-MPI of the fetal right or left heart between pregestational diabetes and gestational diabetes group. Mod-MPI of the right fetal heart is significantly higher in the diabetes group and might have a predictive value of fetal cardiac function associated with the adverse perinatal outcome of diabetic pregnancy.

To provide reference ranges for fetal cardiac parameters by using HeartAssist™, an automated system for measuring such parameters, in 17 large referral centres in South Korea. This prospective study included normal singleton fetuses between 16.0 and 36.6 weeks of gestational age (GA) from October 2022 to February 2023. Video clips of the fetal hearts were collected, and a total of 34 parameters were measured in six cardiac views. In the four chamber view, we measured cardiac axis; thoracic area and circumference; heart area and circumference; atrial widths and areas; ventricular widths, lengths, and areas; and annular diameters of the tricuspid and mitral valves. In the outflow tract view, annular diameters of the aortic and pulmonary valves when open and closed and the diameter of the ascending aorta were measured. In the three vessel view, diameters of the pulmonary artery, aorta, superior vena cava, and thymus were measured. In the three-vessel tracheal view, diameters of the aortic isthmus and ductus arteriosus were measured. In the aortic arch view, the diameters of the ascending aorta, proximal and distal transverse aortic arches, aortic isthmus, and descending aorta were measured. The HeartAssist™ (Samsung Medison Co. Ltd., Seoul, Republic of Korea) was used for all measurements, which were further modified manually by two experts in fetal echocardiography. We analysed video clips from 350 fetuses and designed scatterplots for each parameter according to GA. The cardiac axis was constant throughout gestation, with a mean value of 37.2°. All other parameters increased gradually with advancing GA. The mean ratios of the left ventricular width and length to the right ventricular width and length were 0.96 and 1.09, respectively. Annular diameters of the aortic valve and pulmonary valve were larger when the valves were closed than when open. We established comprehensive reference ranges for fetal cardiac parameters by using HeartAssist™.

the MC twin and the DC twin growth chart, both are significantly smaller than the KSGC, but among them, the MC twin slightly smaller than the DC twin growth chart.The 50 percentile values of the Korean DC twin growth chart and are similar to NICHD but the KTGH has a smaller 90 percent value and a larger 10 percent value than NICHD chart. Conclusions:The KTGH has different patterns from the KSGC, and it has a very similar value to the 50 percentile of NICHD.However, the width of the distribution is narrow compared to the NICHD chart.Korean twins will need to apply a new chart that fits Korean standards clinically.

Supplementary Materials and Methods

To compare the cervical elastographic parameters of singleton and twin pregnancies in asymptomatic pregnant women between 18 and 24 weeks of gestation. This was a multicentre prospective observational study for asymptomatic pregnant women who were scheduled for fetal anomaly scan between 18 and 24 weeks of gestation and had information about pregnancy outcomes. Cervical elastographic parameters were measured using ECervix (WS80A, Samsung Medison, Seoul, Republic of Korea). Exclusion criteria were current progesterone use, placement of cerclage, history of cervical surgery, major fetal anomaly, and symptomatic women related to sPTB. All measurements were performed using our standardised protocol for measuring cervical elastography. A total of 1,604 women (1,464 singletons and 140 twins) were included in this study. Among all elastographic parameters, the strain of the external os of the cervix (EOS) was significantly higher in singletons compared to twins (0.283 ± 0.094 vs. 0.264 ± 0.080, p = 0.022). EOS was significantly higher in the sPTB group compared to the term birth group in twins (0.288 ± 0.065 vs. 0.253 ± 0.088, p = 0.018), but there were no significant differences for EOS in singletons according to sPTB. The strain of internal of the cervix (IOS) showed a higher level (0.246 ± 0.076 vs. 0.223 ± 0.072, p = 0.016), and hardness ratio showed a lower level (70.3 ± 13.9 vs. 74.2 ± 13.1, p = 0.028) in sPTB group compared to term birth group in singleton pregnancies. There was no difference between singleton and twin pregnancies in cervical elastographic parameters other than EOS. There is a difference in cervical elastography in the second trimester between singletons and twins. In addition, the cervical elastographic parameters related to sPTB were different between singleton pregnancy and twin group. (This research was funded by the Korea Health Industry Development Institute (HI18C1696).)

To determine the diagnostic accuracy of coarctation of the aorta (CoA) using several defined z-scores for fetal cardiac parameters, including the new Korean z-scores. This retrospective study included fetuses prenatally suspected with CoA between January 2010 and December 2021 at Asan Medical Center. CoA was suspected prenatally when the z-score of aortic isthmus was < −2 according to previously reported z-scores in the three-vessel-trachea view (3VTV) or sagittal view on fetal echocardiography. Study population were further evaluated whether to be suspected to have CoA using the new Korean z-scores. The final diagnosis was confirmed using echocardiography or cardiac computed tomography performed postbirth. The diagnostic accuracy, Kappa score, and area under the curve (AUC) were compared using different z-scores of aortic isthmus. A total of 228 fetuses were evaluated. On 3VTV, the Korean z-scores of aortic isthmus based on EFW showed the highest diagnostic accuracy of 68.0%, along with Kappa score and AUC (0.4 and 0.73, respectively), indicating higher diagnostic validity compared with previously reported z-scores (0.22 and 0.63, respectively). On sagittal view, Korean z-scores of aortic isthmus based on EFW showed the highest diagnostic accuracy of 57.0%, along with Kappa score and AUC (0.24 and 0.65, respectively), compared with previous findings. Evaluation of aortic isthmus using the new Korean z-scores may improve the diagnostic accuracy of CoA.