Current Trends in Artificial Intelligence-Assisted Spine Surgery: A Systematic Review.

This systematic review summarizes existing evidence and outlines the benefits of artificial intelligence-assisted spine surgery. The popularity of artificial intelligence has grown significantly, demonstrating its benefits in computer-assisted surgery and advancements in spinal treatment. This study adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), a set of reporting guidelines specifically designed for systematic reviews and meta-analyses. The search strategy used Medical Subject Headings (MeSH) terms, including "MeSH (Artificial intelligence)," "Spine" AND "Spinal" filters, in the last 10 years, and English- from January 1, 2013, to October 31, 2023. In total, 442 articles fulfilled the first screening criteria. A detailed analysis of those articles identified 220 that matched the criteria, of which 11 were considered appropriate for this analysis after applying the complete inclusion and exclusion criteria. In total, 11 studies met the eligibility criteria. Analysis of these studies revealed the types of artificial intelligence-assisted spine surgery. No evidence suggests the superiority of assisted spine surgery with or without artificial intelligence in terms of outcomes. In terms of feasibility, accuracy, safety, and facilitating lower patient radiation exposure compared with standard fluoroscopic guidance, artificial intelligence-assisted spine surgery produced satisfactory and superior outcomes. The incorporation of artificial intelligence with augmented and virtual reality appears promising, with the potential to enhance surgeon proficiency and overall surgical safety.

Evaluation of Multiplex Rapid Antigen Tests for the Simultaneous Detection of SARS-CoV-2 and Influenza A/B Viruses.

Single-target rapid antigen tests (RATs) are commonly used to detect highly transmissible respiratory viruses (RVs), such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses. The simultaneous detection of RVs presenting overlapping symptoms is vital in making appropriate decisions about treatment, isolation, and resource utilization; however, few studies have evaluated multiplex RATs for SARS-CoV-2 and other RVs. We assessed the diagnostic performance of multiplex RATs targeting both the SARS-CoV-2 and influenza A/B viruses with the GenBody Influenza/COVID-19 Ag Triple, InstaView COVID-19/Flu Ag Combo (InstaView), STANDARDTM Q COVID-19 Ag Test, and STANDARDTM Q Influenza A/B Test kits using 974 nasopharyngeal swab samples. The cycle threshold values obtained from the real-time reverse transcription polymerase chain reaction results showed higher sensitivity (72.7-100%) when the values were below, rather than above, the cut-off values. The InstaView kit exhibited significantly higher positivity rates (80.21% for SARS-CoV-2, 61.75% for influenza A, and 46.15% for influenza B) and cut-off values (25.57 for SARS-CoV-2, 21.19 for influenza A, and 22.35 for influenza B) than the other two kits, and was able to detect SARS-CoV-2 Omicron subvariants. Therefore, the InstaView kit is the best choice for routine screening for both SARS-CoV-2 and influenza A/B in local communities.

10-year follow-up study on medical expenses and medical care use according to biological age: National Health Insurance Service Health Screening Cohort (NHIS-HealS 2002~2019).

OBJECTIVES: The world is witnessing a sharp increase in its elderly population, accelerated by longer life expectancy and lower birth rates, which in turn imposes enormous medical burden on society. Although numerous studies have predicted medical expenses based on region, gender, and chronological age (CA), any attempt has rarely been made to utilize biological age (BA)-an indicator of health and aging-to ascertain and predict factors related to medical expenses and medical care use. Thus, this study employs BA to predict factors that affect medical expenses and medical care use. MATERIALS AND METHODS: Referring to the health screening cohort database of the National Health Insurance Service (NHIS), this study targeted 276,723 adults who underwent health check-ups in 2009-2010 and kept track of the data on their medical expenses and medical care use up to 2019. The average follow-up period is 9.12 years. Twelve clinical indicators were used to measure BA, while the total annual medical expenses, total annual number of outpatient days, total annual number of days in hospital, and average annual increases in medical expenses were used as the variables for medical expenses and medical care use. For statistical analysis, this study employed Pearson correlation analysis and multiple regression analysis. RESULTS: Regression analysis of the differences between corrected biological age (cBA) and CA exhibited statistically significant increases (p<0.05) in all the variables of the total annual medical expenses, total annual number of outpatient days, total annual number of days in hospital, and average annual increases in medical expenses. CONCLUSIONS: This study quantified decreases in the variables for medical expenses and medical care use based on improved BA, thereby motivating people to become more health-conscious. In particular, this study is significant in that it is the first of its kind to predict medical expenses and medical care use through BA.

Evaluation of Four Rapid Antigen Tests for the Detection of SARS-CoV-2 Infection with Nasopharyngeal Swabs.

Owing to the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the capacity of testing systems based on the gold standard real-time reverse transcription-polymerase chain reaction (rRT-PCR) is limited. Rapid antigen tests (RATs) can substantially contribute to the prevention of community transmission, but their further assessment is required. Here, using 1503 nasopharyngeal swabs, we compared the diagnostic performance of four RAT kits (Abbott Panbio™ COVID-19 Ag Rapid Test, SD Biosensor Standard™ Q COVID-19 Ag Test, Humasis COVID-19 Ag Test, and SG Medical Acrosis COVID-19 Ag Test) to the cycle threshold (Ct) values obtained from rRT-PCR. The precision values, area under the curve values, SARS-CoV-2 variant detection ability, and non-SARS-CoV-2 specificity of all four kits were similar. An assay using the Acrosis kit had a significantly better positive detection rate with a higher recall value and cut-off value than that using the other three RAT kits. During the current COVID-19 pandemic, the Acrosis kit is an effective tool to prevent the spread of SARS-CoV-2 in communities.

Effects of Customized Digital Health Care Service on Metabolic Syndrome Status and Lifestyle Using a Health Care App: Clinical Trial.

BACKGROUND: Untact cultures have rapidly spread around the world as a result of the prolongation of the COVID-19 pandemic, leading to various types of research and technological developments in the fields of medicine and health care, where digital health care refers to health care services provided in a digital environment. Previous studies relating to digital health care demonstrated its effectiveness in managing chronic diseases such as hypertension and diabetes. While many studies have applied digital health care to various diseases, daily health care is needed for healthy individuals before they are diagnosed with a disease. Accordingly, research on individuals who have not been diagnosed with a disease is also necessary. OBJECTIVE: This study aimed to identify the effects of using a customized digital health care service (CDHCS) on risk factors for metabolic syndrome (MS) and lifestyle improvement. METHODS: The population consisted of 63 adults who underwent a health checkup at the National Health Insurance Service Ilsan (NHIS) Hospital in 2020. Measured variables include basic clinical indicators, MS-related variables, and lifestyle variables. All items were measured at NHIS Ilsan Hospital before the use of the CDHCS and 3 months thereafter. The CDHCS used in this study is a mobile app that analyzes the health condition of the user by identifying their risk factors and provides appropriate health care content. For comparison between before and after CDHCS use (pre-post comparison), paired t test was used for continuous variables, and a chi-square test was used for nominal variables. RESULTS: The study population included 30 (47.6%) male and 33 (52.4%) female participants, and the mean age was 47.61 (SD 13.93) years. The changes in clinical indicators before and after intervention results showed a decrease in weight, waist circumference, triglyceride, and high-density lipoprotein cholesterol and increases in systolic blood pressure and diastolic blood pressure. The distribution of the risk group increased from 32 (50.8%) to 34 (54%) and that of the MS group decreased from 18 (28.6%) to 16 (25.4%). The mean metabolic syndrome age-chronological age before the CDHCS was 2.20 years, which decreased to 1.72 years after CDHCS, showing a decrease of 0.48 years in the mean metabolic syndrome age-chronological age after the intervention. While all lifestyle variables, except alcohol consumption, showed a tendency toward improvement, the differences were not statistically significant. CONCLUSIONS: Although there was no statistical significance in the variables under study, this pilot study will provide a foundation for more accurate verification of CDHCS in future research.

An Automated High-Throughput Screening (HTS) Spotter for 3D Tumor Spheroid Formation.

Three-dimensional (3D) culture platforms have been adopted in a high-throughput screening (HTS) system to mimic in vivo physiological microenvironments. The automated dispenser has been established commercially to enable spotting or distributing non-viscous or viscous biomaterials onto microplates. However, there are still challenges to the precise and accurate dispensation of cells embedded in hydrogels such as Alginate- and Matrigel-extracellular matrices. We developed and improved an automated contact-free dispensing machine, the ASFA SPOTTER (V5 and V6), which is compatible with 96- and 384-pillar/well plates and 330- and 532-micropillar/well chips for the support of 3D spheroid/organoid models using bioprinting techniques. This enables the distribution of non-viscous and viscous biosamples, including chemical drugs and cancer cells, for large-scale drug screening at high speed and small volumes (20 to 4000 nanoliters) with no damage to cells. The ASFA SPOTTER (V5 and V6) utilizes a contact-free method that minimizes cross-contamination for the dispensation of encapsulated tissue cells with highly viscous scaffolds (over 70%). In particular, the SPOTTER V6 does not require a washing process and offers the advantage of almost no dead volume (defined as additional required sample volume, including a pre-shot and flushing shot for dispensing). It can be successfully applied for the achievement of an organoid culture in automation, with rapid and easy operation, as well as miniaturization for high-throughput screening. In this study, we report the advantages of the ASFA SPOTTER, which distributes standard-sized cell spots with hydrogels onto a 384-pillar/well plate with a fast dispensing speed, small-scale volume, accuracy, and precision.

Predicting the incidence of age-related diseases based on biological age: The 11-year national health examination data follow-up.

PURPOSE: As the population ages rapidly, the incidence of age-related diseases (ARDs) is also increasing fast. Predicting the incidence of ARDs is a challenge since the rates of individual aging vary, and objective assessments of the stages of aging based on chronological age (CA) may be inaccurate. Thus, in this study, we developed a biological age (BA) model based on the National Health Examination (NHE) data and analyzed the model prediction results for the incidence of 16 ARDs. METHODS: This study was based on the 2002-2019 National Health Information Databases of the National Health Insurance Service (NHIS-NHID). The data from a total of 10,002,494 subjects were selected between 2009 and 2010, and the principal component analysis (PCA) was performed to develop the BA model. The Cox-proportional hazard model was used to perform predictive analysis of the ARD incidence. RESULTS: For the unit increase in the difference between corrected biological age (cBA) and chronological age (CA), the hazard ratios (HRs) of ARDs increased significantly for both sexes (p < 0.001). In descending order, the corresponding ARDs' HRs were obesity (1.655), chronic renal failure (1.362), hypertension (1.301), hyperlipidemia (1.264), diabetes mellitus (1.261), fracture (1.119), dementia (1.163), cataract (1.116), myocardial infarction (1.097), stroke (1.169), macular degeneration (1.075), osteoarthritis (1.059), osteoporosis (1.124), Parkinson's disease (1.048), and chronic obstructive pulmonary disease (1.026). CONCLUSIONS: In this study, the incidence of 16 ARDs were analyzed based on BA. Therefore, conducting the NHIS health examination can facilitate the prevention of ARDs by estimating HRs for at least 16 diseases.

Platelet-to-White Blood Cell Ratio Is Associated with Adverse Outcomes in Cirrhotic Patients with Acute Deterioration.

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9−15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

Comparison of peaks in the matrix-assisted laser desorption ionization time-of-flight mass spectrometry spectra of Staphylococcus aureus grown on various blood agar plates.

Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is routinely used for bacterial identification in clinical laboratories. Bacterial protein expression may differ according to their growth conditions, especially the culture medium composition. We aimed to study the peak variations of Staphylococcus aureus grown on various blood agar plates (BAP), especially phenol-soluble modulin-mec (PSM-mec) peak (m/z 2409) associated with mecA gene conferring methicillin resistance. Methicillin-resistant S. aureus (MRSA) ATCC 43300 and eight clinical MRSA isolates were cultured on various commercial BAPs including tryptic soy agar-based BAPs, Columbia agar-based BAP and in-house BAPs with the addition of yeast extract. Analysis of the MALDI-TOF peaks of S. aureus, cultured on various BAPs, revealed the peak intensities of low-molecular weight proteins to vary depending on the composition of BAPs, especially the presence or absence of yeast extract. Especially, the PSM-mec and delta-toxin peaks showed low intensity for S. aureus ATCC 43300 and clinical isolates. No significant differences were found in the number of peaks, but some peaks had lower intensity, corresponding to the medium containing yeast extract, in low-mass region (< m/z 4000). BAPs based on tryptic soy agar rather than Columbia agar seems to be appropriate for the detection of PSM-mec, a methicillin resistance marker of S. aureus and delta-toxin, an agr function indicator.

Development of an efficient Sanger sequencing-based assay for detecting SARS-CoV-2 spike mutations.

Novel strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) harboring nucleotide changes (mutations) in the spike gene have emerged and are spreading rapidly. These mutations are associated with SARS-CoV-2 transmissibility, virulence, or resistance to some neutralizing antibodies. Thus, the accurate detection of spike mutants is crucial for controlling SARS-CoV-2 transmission and identifying neutralizing antibody-resistance caused by amino acid changes in the receptor-binding domain. Here, we developed five SARS-CoV-2 spike gene primer pairs (5-SSG primer assay; 69S, 144S, 417S, 484S, and 570S) and verified their ability to detect nine key spike mutations (ΔH69/V70, T95I, G142D, ΔY144, K417T/N, L452R, E484K/Q, N501Y, and H655Y) using a Sanger sequencing-based assay. The 5-SSG primer assay showed 100% specificity and a conservative limit of detection with a median tissue culture infective dose (TCID50) values of 1.4 × 102 TCID50/mL. The accuracy of the 5-SSG primer assay was confirmed by next generation sequencing. The results of these two approaches showed 100% consistency. Taken together, the ability of the 5-SSG primer assay to accurately detect key SARS-CoV-2 spike mutants is reliable. Thus, it is a useful tool for detecting SARS-CoV-2 spike gene mutants in a clinical setting, thereby helping to improve the management of patients with COVID-19.

Antiviral Activity of Two Marine Carotenoids against SARS-CoV-2 Virus Entry In Silico and In Vitro.

The marine carotenoids fucoxanthin and siphonaxanthin are powerful antioxidants that are attracting focused attention to identify a variety of health benefits and industry applications. In this study, the binding energy of these carotenoids with the SARS-CoV-2 Spike-glycoprotein was predicted by molecular docking simulation, and their inhibitory activity was confirmed with SARS-CoV-2 pseudovirus on HEK293 cells overexpressing angiotensin-converting enzyme 2 (ACE2). Siphonaxanthin from Codium fragile showed significant antiviral activity with an IC50 of 87.4 µM against SARS-CoV-2 pseudovirus entry, while fucoxanthin from Undaria pinnatifida sporophyll did not. The acute toxicities were predicted to be relatively low, and pharmacokinetic predictions indicate GI absorption. Although further studies are needed to elucidate the inhibition of viral infection by siphonaxanthin, these results provide useful information in the application of these marine carotenoids for the treatment and prevention of COVID-19.

Inhibition of SARS-CoV-2 Virus Entry by the Crude Polysaccharides of Seaweeds and Abalone Viscera In Vitro.

Much attention is being devoted to the potential of marine sulfated polysaccharides as antiviral agents in preventing COVID-19. In this study, sulfated fucoidan and crude polysaccharides, extracted from six seaweed species (Undaria pinnatifida sporophyll, Laminaria japonica, Hizikia fusiforme, Sargassum horneri, Codium fragile, Porphyra tenera) and Haliotis discus hannai (abalone viscera), were screened for their inhibitory activity against SARS-CoV-2 virus entry. Most of them showed significant antiviral activities at an IC50 of 12~289 µg/mL against SARS-CoV-2 pseudovirus in HEK293/ACE2, except for P. tenera (IC50 > 1000 µg/mL). The crude polysaccharide of S. horneri showed the strongest antiviral activity, with an IC50 of 12 µg/mL, to prevent COVID-19 entry, and abalone viscera and H. fusiforme could also inhibit SARS-CoV-2 infection with an IC50 of 33 µg/mL and 47 µg/mL, respectively. The common properties of these crude polysaccharides, which have strong antiviral activity, are high molecular weight (>800 kDa), high total carbohydrate (62.7~99.1%), high fucose content (37.3~66.2%), and highly branched polysaccharides. These results indicated that the crude polysaccharides from seaweeds and abalone viscera can effectively inhibit SARS-CoV-2 entry.

Characterization of Chlamydia trachomatis ompA Genotypes Among Sexually Transmitted Disease Patients in Korea.

BACKGROUND: Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases (STDs) world-wide. The aim of this study was to characterize the C. trachomatis genetic profiles of clinical isolates in the Korean population by sequence analysis of the ompA gene. METHODS: Endocervical specimens from patients who were confirmed as C. trachomatis infection by real-time PCR were used for ompA sequencing. The individual sequences (about 890 nucleotides) were determined by comparison with those from known C. trachomatis strains using the BLAST search tool. Sequence variations were analyzed by comparing them with sequences from prototype strains. RESULTS: Sequence analysis using BLAST similarity search of the ompA gene from the 106 clinical isolates revealed that the most prevalent genotype corresponded to E (n = 28, 26.2%), followed by F (n = 20, 18.9%), D (n = 16, 15.1%), J (n = 16, 15.1%), G (n = 9, 8.5%), H (n = 8, 7.5%), K (n = 5, 4.7%), B (n = 2, 1.9%), and I (n = 2, 1.9%). Detailed sequence analysis based on comparison with each prototype revealed that there are sequence differences in 44 specimens (41.5%). CONCLUSIONS: This study is the update on the distribution of C. trachomatis ompA genotypes in Korea in more than a decade. The genotypes have become more diversified, with genotypes K, B, and I being newly detected. C. trachomatis genotyping is crucial for regional and global epidemiological studies, as well as for vaccine development.

Rapid Discrimination of Methicillin-Resistant Staphylococcus aureus by MALDI-TOF MS.

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious pathogen in clinical settings and early detection is critical. Here, we investigated the MRSA discrimination potential of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) using 320 clinical S. aureus isolates obtained in 2005-2014 and 181 isolates obtained in 2018. We conducted polymerase chain reactions (PCR) for staphylococcal cassette chromosome mec (SCCmec) typing and MALDI-TOF MS to find specific markers for methicillin resistance. We identified 21 peaks with significant differences between MRSA and methicillin-susceptible S. aureus (MSSA), as determined by mecA and SCCmec types. Each specific peak was sufficient to discriminate MRSA. We developed two methods for simple discrimination according to these peaks. First, a decision tree for MRSA based on six MRSA-specific peaks, three MSSA-specific peaks, and two SCCmec type IV peaks showed a sensitivity of 96.5%. Second, simple discrimination based on four MRSA-specific peaks and one MSSA peak had a maximum sensitivity of 88.3%. The decision tree applied to 181 S. aureus isolates from 2018 had a sensitivity of 87.6%. In conclusion, we used specific peaks to develop sensitive MRSA identification methods. This rapid and easy MALDI-TOF MS approach can improve patient management.

A comparative evaluation of BACT/ALERT FA PLUS and FN PLUS blood culture bottles and BD BACTEC Plus Aerobic and Anaerobic blood culture bottles for antimicrobial neutralization.

The performance of BACT/ALERT FA and FN PLUS (FA PLUS and FN PLUS) blood culture bottles with the BACT/ALERT VIRTUO (bioMérieux, Inc., Durham, NC) and BD BACTEC Plus Aerobic and Anaerobic (BD Aerobic and BD Anaerobic) blood culture bottles with the BD BACTEC FX (BD Diagnostics, Sparks, MD) for antimicrobial neutralization at peak serum concentration was evaluated. The following antibiotic agents and microbial strains were used: ampicillin, cefepime, cefotaxime, gentamicin, levofloxacin, meropenem, piperacillin-tazobactam, and vancomycin; methicillin-sensitive Staphylococcus aureus, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Bacteroides fragilis. The detection rate of FA PLUS bottles was 69.1% (259/375) and that of BD Aerobic bottles was 75.5% (283/375) (p = 0.050). In the case of anaerobic culture, the overall detection rate of FN PLUS bottles was 77.0% (231/300) and that of BD Anaerobic bottles was 71.3% (214/300) (p = 0.113). The time to detection (TTD) from aerobic culture was 2.8 h shorter in FA PLUS bottles (12.4 h) compared to BD Aerobic bottles (15.2 h) (p < 0.001). And the TTD from anaerobic culture was 1.6 h shorter in FN PLUS bottles (18.1 h) compared to BD Anaerobic bottles (19.7 h) (p = 0.061). The FA PLUS bottles exhibited a lower detection rate compared to BD Aerobic bottles, while FN PLUS bottles showed a higher detection rate compared to BD Anaerobic bottles. The BACT/ALERT VIRTUO system exhibited shorter TTD compared to the BD BACTEC FX system for both aerobic and anaerobic cultures.

Background and Activities of the Samsung Ombudsperson Commission in Korea.

OBJECTIVES: The Samsung Ombudsperson Commission was launched as an independent third-party institution following an agreement among Samsung Electronics, Supporters for Health and Right of People in Semiconductor Industry (Banolim in Korean, an independent NGO), and the Family Compensation Committee, in accordance with the industry accident prevention measure required by the settlement committee to address the issues related to employees who allegedly died from leukemia and other diseases as a result of working at Samsung's semiconductor production facilities. METHODS: The Commission has carried out a comprehensive range of activities to review and evaluate the status of the company's occupational accidents management system, as well as occupational safety and health risk management within its facilities. RESULTS: Based on the results of this review, termed a comprehensive diagnosis, the Commission presented action plans for improvement to strengthen the company's existing safety and health management system and to effectively address uncertain risks in this area going forward. CONCLUSIONS: The Commission will monitor the execution of the suggested tasks and provide advice and guidance to ensure that Samsung's semiconductor and liquid crystal display production lines are safer.

Effectiveness of the computerized balance rehabilitation after hip fracture surgery: A study protocol of a prospective and open-label clinical trial.

INTRODUCTION: Although balance problems in older populations are directly correlated with hip fractures, the overall physical gain afforded by balance rehabilitation itself has not yet been fully investigated. Here we describe a protocol for an open-label clinical trial to evaluate the effectiveness of computer-based balance-specific exercise (BSE) on the performance and balance of elderly women who underwent hip fracture surgery (HFS). METHODS AND ANALYSIS: Elderly female patients (≥65 years old) who underwent surgery for femoral neck, intertrochanteric, or subtrochanteric fracture regardless of surgery type will be included. The BSE will be conducted using a computed posturographic system for a 2-week intervention period following HFS. The primary outcome of this study is Berg balance scale score. All functional outcomes will be measured at 1 and 3 weeks and at 3 and 6 months after the surgical intervention. The data will be analyzed using the intention-to-treat principle.

YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner.

Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)-dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development.

Creatine inhibits adipogenesis by downregulating insulin-induced activation of the phosphatidylinositol 3-kinase signaling pathway.

Creatine is a nitrogenous organic acid known to function in adenosine triphosphate (ATP) metabolism. Recent evidence indicates that creatine regulates the differentiation of mesenchymal stem cells (MSCs) in processes such as osteogenesis and myogenesis. In this study, we show that creatine also has a negative regulatory effect on fat cell formation. Creatine inhibits the accumulation of cytoplasmic triglycerides in a dose-dependent manner irrespective of the adipogenic cell models used, including a C3H10T1/2 MSC line, 3T3-L1 preadipocytes, and primary human MSCs. Consistently, a dramatic reduction in mRNA expression of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), glucose transporters, 1 and 4 (Glut1, Glut4), and adipocyte markers, aP2 and adipsin, was observed in the presence of creatine. Creatine appears to exert its inhibitory effects on adipogenesis during early differentiation, but not late differentiation, or proliferation stages through inhibition of the PI3K-Akt-PPARγ signaling pathway. In an in vivo model, administration of creatine into mice resulted in body mass increase without fat accumulation. In summary, our results indicate that creatine downregulates adipogenesis through inhibition of phosphatidylinositol 3-kinase (PI3K) activation and imply the potent therapeutic value of creatine in treating obesity and obesity-related metabolic disorders.

Notch intracellular domain deficiency in nuclear localization activity retains the ability to enhance neural stem cell character and block neurogenesis in mammalian brain development.

Notch has a broad range of regulatory functions in many developmental processes, including hematopoiesis, neurogenesis, and angiogenesis. Notch has several key functional regions such as the RBP-Jκ/CBF1 association module (RAM) domain, nuclear localization signals (NLS), and ankyrin (ANK) repeats. However, previous reports assessing the level of importance of these domains in the Notch signaling pathway are controversial. In this study, we have assessed the level of contribution of each Notch domain to the regulation of mammalian neural stem cells in vivo as well as in vitro. Reporter assays and real-time polymerase chain reactions show that the ANK repeats and RAM domain are indispensable to the transactivation of Notch target genes, whereas a nuclear export signal (NES)-fused Notch intracellular domain (NICD) mutant defective in nuclear localization exerts a level of activity comparable to unmodified NICD. Transactivational ability appears to be tightly coupled to Notch functions during brain development. Unlike ANK repeats and RAM domain deletion mutants, NES-NICD recapitulates NICD features such as promotion of astrogenesis at the expense of neurogenesis in vitro and enhancement of neural stem cell character in vivo. Our data support the previous observation that intranuclear localization is not essential to the oncogenesis of Notch1 in certain types of cells and imply the importance of the noncanonical Notch signaling pathway in the regulation of mammalian neural stem cells.