Spatially resolved whole-transcriptomic and proteomic profiling of lung cancer and its immune-microenvironment according to PD-L1 expression.

The expression of PD-L1 on tumor cells (TCs) is used as an immunotherapy biomarker in lung cancer, but heterogeneous intratumoral expression is often observed. Using a Digital Spatial Profiling, we performed proteomic and whole-transcriptomic analyses of TCs and immune cells (ICs) in spatially matched areas based on tumor PD-L1 expression and the status of the immune microenvironment. Our findings were validated using immunohistochemistry, The Cancer Genome Atlas, and immunotherapy cohorts. ICs in areas with high PD-L1 expression on TCs showed more features indicative of immunosuppression and exhaustion than ICs in areas with low PD-L1 expression on TCs. TCs highly expressing PD-L1 within immune-inflamed (IF) areas show up-regulation of pro-inflammatory processes, whereas TCs highly expressing PD-L1 within immune-deficient (ID) areas show up-regulation of various metabolic processes. Using differentially expressed genes of TCs between the IF and ID areas, we identified a novel prognostic gene signature for lung cancer. In addition, a high ratio of CD8+ cells to M2 macrophages was found to predict favorable outcomes in patients with PD-L1-expressing lung cancer after immune checkpoint inhibitor therapy. This study demonstrates that TCs and ICs have distinct spatial features within the tumor microenvironment that are related to tumor PD-L1 expression and IC infiltration.

Optimizing Data-Centric Healthcare: A Novel Monitoring Framework for High-Risk General Ward Patients.

The digital transformation of healthcare in South Korea, accelerated by COVID-19, has led to increased focus on critically ill patients in large hospitals. To address this, a monitoring system was developed to ensure safe inpatient treatment and improve staff efficiency. This aligns with the Medical Data-Centric Hospitals initiative, which leverages data for healthcare innovation. The case study highlights the implementation of a ward critical care monitoring system, which has improved patient safety, work efficiency, and expanded patient monitoring scope. Key lessons include the importance of addressing technical and user challenges, aligning innovations with national policies, and the potential of data-driven solutions to tackle healthcare challenges.

Selecting serum-free hepatocyte cryopreservation stage and storage temperature for the application of an "off-the-shelf" bioartificial liver system.

The bioartificial liver (BAL) system can potentially rescue acute liver failure (ALF) patients by providing partial liver function until a suitable donor liver can be found or the native liver has self-regenerated. In this study, we established a suitable cryopreservation process for the development of an off-the-shelf BAL system. The viability of hepatocyte spheroids cryopreserved in liquid nitrogen was comparable to that of fresh primary hepatocyte spheroids. When hepatocyte spheroids were subjected to cryopreservation in a deep freezer, no statistically significant differences were observed in ammonia removal rate or urea secretion rate based on the cryopreservation period. However, the functional activity of the liver post-cryopreservation in a deep freezer was significantly lower than that observed following liquid nitrogen cryopreservation. Moreover, cryopreserving spheroid hydrogel beads in a deep freezer resulted in a significant decrease (approximately 30%) in both ammonia removal and urea secretion rates compared to the group cryopreserved in liquid nitrogen. The viabilities of spheroid hydrogel beads filled into the bioreactor of a BAL system were similar across all four groups. However, upon operating the BAL system for 24 h, the liver function activity was significantly higher in the group comprising hydrogel beads generated after thawing hepatocyte spheroids cryopreserved in liquid nitrogen. Consequently, the manufacturing of beads after the cryopreservation of hepatocyte spheroids is deemed the most suitable method, considering efficiency, economic feasibility, and liver function activity, for producing a BAL system.

Characterization of a new selective glucocorticoid receptor modulator with anorexigenic activity.

Obesity, a worldwide epidemic, leads to various metabolic disorders threatening human health. In response to stress or fasting, glucocorticoid (GC) levels are elevated to promote food intake. This involves GC-induced expression of the orexigenic neuropeptides in agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus (ARC) via the GC receptor (GR). Here, we report a selective GR modulator (SGRM) that suppresses GR-induced transcription of genes with non-classical glucocorticoid response elements (GREs) such as Agrp-GRE, but not with classical GREs, and via this way may serve as a novel anti-obesity agent. We have identified a novel SGRM, 2-O-trans-p-coumaroylalphitolic acid (Zj7), a triterpenoid extracted from the Ziziphus jujube plant, that selectively suppresses GR transcriptional activity in Agrp-GRE without affecting classical GREs. Zj7 reduces the expression of orexigenic genes in the ARC and exerts a significant anorexigenic effect with weight loss in both high fat diet-induced obese and genetically obese db/db mouse models. Transcriptome analysis showed that Zj7 represses the expression of a group of orexigenic genes including Agrp and Npy induced by the synthetic GR ligand dexamethasone (Dex) in the hypothalamus. Taken together, Zj7, as a selective GR modulator, showed beneficial metabolic activities, in part by suppressing GR activity in non-classical GREs in orexigenic genes. This study demonstrates that a potential anorexigenic molecule may allow GRE-specific inhibition of GR transcriptional activity, which is a promising approach for the treatment of metabolic disorders.

Seeding recurrence of follicular thyroid carcinoma after transoral endoscopic thyroidectomy vestibular approach: a case report.

Background: While track recurrence of thyroid cancer following endoscopic and robotic transaxillary surgeries has been reported previously, no such cases have been reported for transoral endoscopic thyroidectomy vestibular approach (TOETVA). This case report describes the first documented case of recurrence of thyroid cancer along the surgical track after TOETVA. Case Description: The patient underwent right lobectomy via TOETVA for a 4 cm follicular thyroid carcinoma (FTC) initially diagnosed as benign follicular nodule on preoperative gun biopsy. The thyroid capsule partially ruptured within the surgical field during surgery. Ultrasonography and computed tomography conducted 27 months after surgery revealed seeding recurrence in the postsurgical thyroid bed, and subcutaneous layers of the right lower lip, submental area, and mid to right upper neck levels I, IIA, and VI. Two-stage re-operation was done to perform completion thyroidectomy, lymph node dissection, and excision of recurrent nodules, which were pathologically confirmed as metastatic FTC. The patient underwent two treatments of radioactive iodine therapy, and post-therapeutic whole-body scintigraphy and computed tomography showed no residual disease. Conclusions: Careful monitoring after TOETVA is essential due to the rare but potential risk of seeding recurrence, especially when the thyroid gland ruptures during surgery. Surgeons should be aware of this atypical complication and be prepared to recommend surgical and/or medical strategies to manage any local seeding of thyroid tissue that may occur.

Clinicopathological implications of immunohistochemical expression of TBX21, CXCR3, GATA3, CCR4, and TCF1 in nodal follicular helper T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified.

BACKGROUND: The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1- and Th2-like molecules in nodal PTCL is unclear. METHODS: Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)/nodal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-Tfh/nTFHL-not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed. RESULTS: TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/ nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-Tfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054). CONCLUSIONS: The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

Intranasal mRNA Delivery via Customized RNA-Polyplex Nanoparticles Enhancing Gene Expression through Photochemical Mechanisms.

Achieving effective mRNA expression in vivo requires careful selection of an appropriate delivery vehicle and route of administration. Among the various routes of administration, intranasal administration has received considerable attention due to its ability to induce potent immune responses. In this context, we designed a specialized cationic polymer tailored for delivery of mRNA into the nasal cavity. These polymers are designed with varying degrees of substitution in different amine groups to allow for identification of the most suitable amine moiety for effective mRNA delivery. We also incorporated a photosensitizer within the polymer structure that can trigger the generation of reactive oxygen species when exposed to light. The synthesized cationic polymer is complexed with anionic mRNA to form a polyplex. Illuminating these polyplexes with laser light enhances their escape from intracellular endosomes, stimulating mRNA translocation into the cytoplasm, followed by increased mRNA expression at the cellular level. Through intranasal administration to C57BL/6 mice, it was confirmed that these photoactive polyplexes effectively induce mRNA expression and activate immune responses in vivo using photochemical effects. This innovative design of a photoactivated cationic polymer presents a promising and reliable strategy to achieve efficient intranasal mRNA delivery. This approach has potential applications in the development of mRNA-based vaccines for both prophylactic and therapeutic purposes.

Change in Severity and Clinical Manifestation of MIS-C Over SARS-CoV-2 Variant Outbreaks in Korea.

BACKGROUND: There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea. METHODS: We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020-May 2021; delta period as June 2021-December 2021; and omicron period as January 2022-April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period. RESULTS: A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1-83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2-2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs. CONCLUSION: Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.

Factors associated with Pap test screening among South Korean women aged 20 to 39 years.

The number of hospital visits with cervical cancer as the chief complaint among South Korean women aged 20 to 39 has increased by 1.2 times between 2016 and 2020, indicating a need for active screening for the disease. This study aimed to investigate the status of the Papanicolaou (Pap) test and identify factors influencing Pap test experience among South Korean women aged 20 to 39 years. An online questionnaire survey was conducted over 5 days starting from November 19, 2021. A total of 338 participants who were randomly sampled by age completed the survey. Data were analyzed using descriptive statistics, t test, χ2 test, and logistic regression. The mean age of the participants was 29.9 years, and participants with and without Pap test experience accounted for 60.7% and 39.3% of the total, respectively. There were significant differences in age, marital status, employment status, smoking status, experience of coitus, awareness of the National Cancer Screening Program, and human papillomavirus (HPV) vaccination status according to the Pap test experience (P < .05) of the participants. Pap test attitude, Pap test self-efficacy, cervical cancer knowledge, HPV knowledge, and cancer prevention behavior scores were significantly higher in the Pap test experience group than in the no Pap test experience group (P < .05). Logistic regression analysis showed that experience of coitus (odds ratio [OR] = 10.46, 95% confidence interval [CI]: 4.54-24.11), marital status (OR = 5.96, 95% CI: 2.25-15.77), awareness of the National Cancer Screening Program (OR = 4.39, 95% CI: 1.66-11.58), HPV vaccination (OR = 2.62, 95% CI: 1.35-5.09), employment status (OR = 2.22, 95% CI: 1.08-4.59), and self-efficacy (OR = 1.09, 95% CI: 1.01-1.19) were the influencing factors in the Pap test experience group. To improve the Pap test screening rate among South Korean women aged 20 to 39, reinforcement strategies and intervention programs that involve age-specific approaches must be established.

Investigation of optimal convolutional neural network conditions for thyroid ultrasound image analysis.

Neural network models have been used to analyze thyroid ultrasound (US) images and stratify malignancy risk of the thyroid nodules. We investigated the optimal neural network condition for thyroid US image analysis. We compared scratch and transfer learning models, performed stress tests in 10% increments, and compared the performance of three threshold values. All validation results indicated superiority of the transfer learning model over the scratch model. Stress test indicated that training the algorithm using 3902 images (70%) resulted in a performance which was similar to the full dataset (5575). Threshold 0.3 yielded high sensitivity (1% false negative) and low specificity (72% false positive), while 0.7 gave low sensitivity (22% false negative) and high specificity (23% false positive). Here we showed that transfer learning was more effective than scratch learning in terms of area under curve, sensitivity, specificity and negative/positive predictive value, that about 3900 images were minimally required to demonstrate an acceptable performance, and that algorithm performance can be customized according to the population characteristics by adjusting threshold value.

Pediatric management challenges of hyperglycemic hyperosmolar state: case series of Korean adolescents with type 2 diabetes.

The hyperglycemic hyperosmolar state (HHS) is considered the most fatal complication of type 2 diabetes mellitus (DM). The number of case reports describing pediatric HHS has increased recently in parallel with obesity and the prevalence of type 2 DM in pediatric patients. In this study, we investigated the patient characteristics and outcomes of HHS in 9 adolescents with obesity and type 2 DM. Almost all patients exhibited mixed clinical features of HHS and diabetic ketoacidosis (DKA), including characteristics such as hyperosmolality and ketoacidosis. These features made definitive diagnosis difficult; 5 out of 9 patients were initially diagnosed with DKA and were treated accordingly. Patients who were initially diagnosed with HHS received a more vigorous and appropriate fluid replacement than other patients did. No patients died, although 3 exhibited complications, such as arrhythmia, acute kidney injury requiring renal replacement therapy, rhabdomyolysis, and acute pancreatitis. Hyperosmolality with consequent severe dehydration is considered a significant factor contributing to the outcomes of patients with HHS. Therefore, early recognition of hyperosmolality is crucial for an appropriate diagnosis and adequate fluid rehydration to restore perfusion in the early period of treatment to improve patient outcomes for this rare but serious emerging condition in pediatric patients.

Establishment of a Serum-Free Hepatocyte Cryopreservation Process for the Development of an "Off-the-Shelf" Bioartificial Liver System.

To use hepatocytes immediately when necessary for hepatocyte transplantation and bioartificial liver (BAL) systems, a serum-free cryopreservation protocol ensuring the high survival of hepatocytes and maintenance of their functions should be developed. We established a serum-free protocol for the cryopreservation of primary hepatocytes, hepatocyte spheroids, and hepatocyte spheroid beads in liquid nitrogen. The serum-free cryopreservation solutions showed a significantly higher performance in maintaining enhanced viability and ammonia removal, urea secretion, and the albumin synthesis of hepatocyte spheroids and spheroid beads. The serum-free thawing medium, containing human serum albumin (HSA) and N-acetylcysteine (NAC), was compared with a fetal bovine serum-containing thawing medium for the development of a serum-free thawing medium. Our results show that hepatocyte spheroids and spheroid beads thawed using a serum-free thawing medium containing HSA and NAC exhibited increased hepatocyte viability, ammonia removal, urea secretion, and albumin synthesis compared to those thawed using the serum-containing medium. Finally, we evaluated the liver functions of the cryopreserved BAL system-applied serum-free cryopreservation process compared to the fresh BAL system. The ammonia removal efficiency of the cryopreserved hepatocyte spheroids BAL was lower than or similar to that of the fresh BAL system. Additionally, the urea concentrations in the media of all three BAL systems were not significantly different during BAL system operation. This cryopreserved spheroid-based BAL system using a serum-free process will be a good candidate for the treatment of patients.

Multicenter validation of a deep-learning-based pediatric early-warning system for prediction of deterioration events.

BACKGROUND: Early recognition of deterioration events is crucial to improve clinical outcomes. For this purpose, we developed a deep-learning-based pediatric early-warning system (pDEWS) and aimed to validate its clinical performance. METHODS: This is a retrospective multicenter cohort study including five tertiary-care academic children's hospitals. All pediatric patients younger than 19 years admitted to the general ward from January 2019 to December 2019 were included. Using patient electronic medical records, we evaluated the clinical performance of the pDEWS for identifying deterioration events defined as in-hospital cardiac arrest (IHCA) and unexpected general ward-to-pediatric intensive care unit transfer (UIT) within 24 hours before event occurrence. We also compared pDEWS performance to those of the modified pediatric early-warning score (PEWS) and prediction models using logistic regression (LR) and random forest (RF). RESULTS: The study population consisted of 28,758 patients with 34 cases of IHCA and 291 cases of UIT. pDEWS showed better performance for predicting deterioration events with a larger area under the receiver operating characteristic curve, fewer false alarms, a lower mean alarm count per day, and a smaller number of cases needed to examine than the modified PEWS, LR, or RF models regardless of site, event occurrence time, age group, or sex. CONCLUSIONS: The pDEWS outperformed modified PEWS, LR, and RF models for early and accurate prediction of deterioration events regardless of clinical situation. This study demonstrated the potential of pDEWS as an efficient screening tool for efferent operation of rapid response teams.

Witnessing Risky Behaviors in Workplaces and Predictors of Sexual Violence Awareness.

To investigate the levels of witnessing risky behaviors in workplaces, such as sexual violence, and identify the factors associated with sexual violence awareness among employees. An online survey was conducted on 336 workers (aged 20-65 years), registered in an online survey company in Korea. The survey was conducted from September 15, 2021, to September 17, 2021. The participants were divided into equal quotas sampled on the basis of sex and age (participants' average age was 44 years, among whom 171 were women [50.9%] and 165 were men [49.1%]). The questionnaire contained items pertaining to demographic characteristics, gender consciousness, sexual violence awareness, witness experience, situational empathy distress, self-efficacy, and self-esteem. The collected data were analyzed using descriptive statistics, Pearson's correlation analysis, and multiple regression. Sexual violence awareness was lower among male workers than among female workers (P < .001), and sexual harassment and violence accounted for 54.8% of cases witnessed. The predictors of sexual violence awareness were age, gender consciousness, situational empathy, and self-esteem, with these factors explaining 53.9% of the variance. The findings highlight the need for strategies to improve sexual violence awareness and bystander intervention that are tailored to demographic predictors, such as sex, age, total length of employment, and position. These results could provide foundational data for developing sexual violence prevention education programs and practical bystander intervention programs focused on coworkers as well as promote relevant policymaking.

A Meta-Analysis of Factors Related to Job Satisfaction: Focused on Korean Nurses.

Background: Nurses comprise the majority of the healthcare workforce, and their job satisfaction can have a substantial impact on patient health. Methods: This study aimed to provide a comprehensive overview of studies that performed statistical analyses focused on the job satisfaction of nurses and relevant factors, as well as synthesizing existing data. Overall, 144 studies published between 1986 and 2018 were reviewed for qualitative synthesis. Results: The most frequently measured variable was job stress, followed by burnout and turnover intention. Overall, 53 studies published between 1994 and 2018 were reviewed for quantitative synthesis. In the meta-analysis, the weighted mean effect size using a random-effects model was moderate for all variables: -0.539, -0.484, and -0.395 for burnout, turnover intention, and job stress, respectively. Conclusion: The results revealed a long history of variables related to job satisfaction among Korean nurses since data retrieval was not subject to any restrictions. These findings can be used as evidence for the formulation of policies to enhance the retention of nurses committed to their profession. Further, they can facilitate stable workforce management in healthcare.

Efficacy of Parenting Programs to Reduce Parenting Burdens in Multicultural Families: A Systematic Review and Meta-Analysis.

Background: We comprehensively investigated and summarized the current situation of parenting programs for multicultural families in South Korea. Methods: Two researchers independently searched and selected 16 studies on parenting programs for multicultural families and analyzed the major dependent variables, including parenting stress, parenting efficacy, parenting attitude, and parental satisfaction, in a meta-analysis of parenting stress and parenting efficacy (n=6 each). This study was dealt with a Bayesian meta-analysis to perform examine the effect sizes for parenting stress and parenting efficacy. Sensitivity to prior distributions was evaluated before the Bayesian meta-analysis, and an optimal prior distribution was selected based on the Watanabe-Akaike information criterion. Results: The combined effect sizes for parenting stress and parenting efficacy were found to be >1 in both the frequentist and Bayesian meta-analyses, indicating that the parenting programs for multicultural families in South Korea are highly effective. Conclusion: These basic data can facilitate the expansion of customized social services for reducing parenting burdens in multicultural families.

TCF1+PD-1+ tumour-infiltrating lymphocytes predict a favorable response and prolonged survival after immune checkpoint inhibitor therapy for non-small-cell lung cancer.

BACKGROUND: T-cell factor 1 (TCF1)+Programmed cell death-1 (PD-1)+ tumour-infiltrating lymphocytes (TILs) are a recently defined subset of exhausted T-cells (Texh-cells) that exhibit a progenitor phenotype. They have been associated with a response to immune checkpoint inhibitor (ICI) therapy in murine tumour models and in patients with malignant melanoma. We investigated the significance of TCF1+PD-1+ TILs as a predictive biomarker for ICI therapy response in non-small-cell lung cancer (NSCLC). METHODS: Two different cohorts of NSCLC patients treated with ICI targeting the PD-1/PD-L1 pathway were included. RNA-seq was performed using NSCLC tissues obtained from 234 patients prior to immunotherapy (RNA-seq cohort). Double immunostaining of TCF1 and PD-1 and single immunostaining of other immunologic markers were performed in resected tumour tissues from another 116 patients (immunohistochemistry cohort). RESULTS: In the RNA-seq cohort, both Texh-cell and progenitor Texh-cell gene sets were enriched in responders compared with non-responders. Larger Texh-cell fractions and increased progenitor Texh-cell gene sets were significantly associated with better progression-free survival (PFS). In the immunohistochemistry cohort, the TCF1+PD-1+ TIL number and PD-L1 tumour proportion score were significantly higher in responders than in non-responders. A high number of TCF1+PD-1+ TILs was significantly associated with both PFS and overall survival (OS) after ICI therapy, and it independently predicted a better PFS and OS according to multivariate analysis. CONCLUSION: TCF1+PD-1+ TILs, representing progenitor Texh-cells, predict both better response and survival in NSCLC patients after ICI therapy. Thus, they may be a useful predictive biomarker for ICI therapy in NSCLC.

Fat3 regulates neural progenitor cells by promoting Yap activity during spinal cord development.

Early embryonic development of the spinal cord requires tight coordination between proliferation of neural progenitors and their differentiation into distinct neuronal cell types to establish intricate neuronal circuits. The Hippo pathway is one of the well-known regulators to control cell proliferation and govern neural progenitor cell number, in which the downstream effector Yes-associated protein (Yap) promotes cell cycle progression. Here we show that an atypical cadherin Fat3, expressed highly in the neural tube, plays a critical role in maintaining proper number of proliferating progenitors. Knockdown of Fat3 in chick neural tube down-regulates expression of the proliferation markers but rather induces the expression of neural markers in the ventricular zone. We further show that deletion of Fat3 gene in mouse neural tube depletes neural progenitors, accompanied by neuronal gene expression in the ventral ventricular zone of the spinal cord. Finally, we found that Fat3 regulates the phosphorylation level of Lats1/2, the upstream kinase of Yap, resulting in dephosphorylation and stabilization of Yap, suggesting Yap as a key downstream effector of Fat3. Our study uncovers another layer of regulatory mechanisms in controlling the activity of Hippo signaling pathway to regulate the size of neural progenitor pools in the developing spinal cord.