A multi-scale map of cell structure fusing protein images and interactions.

The cell is a multi-scale structure with modular organization across at least four orders of magnitude1. Two central approaches for mapping this structure-protein fluorescent imaging and protein biophysical association-each generate extensive datasets, but of distinct qualities and resolutions that are typically treated separately2,3. Here we integrate immunofluorescence images in the Human Protein Atlas4 with affinity purifications in BioPlex5 to create a unified hierarchical map of human cell architecture. Integration is achieved by configuring each approach as a general measure of protein distance, then calibrating the two measures using machine learning. The map, known as the multi-scale integrated cell (MuSIC 1.0), resolves 69 subcellular systems, of which approximately half are to our knowledge undocumented. Accordingly, we perform 134 additional affinity purifications and validate subunit associations for the majority of systems. The map reveals a pre-ribosomal RNA processing assembly and accessory factors, which we show govern rRNA maturation, and functional roles for SRRM1 and FAM120C in chromatin and RPS3A in splicing. By integration across scales, MuSIC increases the resolution of imaging while giving protein interactions a spatial dimension, paving the way to incorporate diverse types of data in proteome-wide cell maps.

Self-organizing in vitro mouse neural tube organoids mimic embryonic development.

The embryonic neural tube is the origin of the entire adult nervous system, and disturbances in its development cause life-threatening birth defects. However, the study of mammalian neural tube development is limited by the lack of physiologically realistic three-dimensional (3D) in vitro models. Here, we report a self-organizing 3D neural tube organoid model derived from single mouse embryonic stem cells that exhibits an in vivo-like tissue architecture, cell type composition and anterior-posterior (AP) patterning. Moreover, maturation of the neural tube organoids showed the emergence of multipotent neural crest cells and mature neurons. Single-cell transcriptome analyses revealed the sequence of transcriptional events in the emergence of neural crest cells and neural differentiation. Thanks to the accessibility of this model, phagocytosis of migrating neural crest cells could be observed in real time for the first time in a mammalian model. We thus introduce a tractable in vitro model to study some of the key morphogenetic and cell type derivation events during early neural development.

An epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer.

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.

Characterization of Phytoplankton-Derived Amino Acids and Tracing the Source of Organic Carbon Using Stable Isotopes in the Amundsen Sea.

We utilized amino acid (AA) and carbon stable isotope analyses to characterize phytoplankton-derived organic matter (OM) and trace the sources of organic carbon in the Amundsen Sea. Carbon isotope ratios of particulate organic carbon (δ13C-POC) range from -28.7‱ to -23.1‱, indicating that particulate organic matter originated primarily from phytoplankton. The dissolved organic carbon isotope (δ13C-DOC) signature (-27.1 to -21.0‱) observed in the sea-ice melting system suggests that meltwater contributes to the DOC supply of the Amundsen Sea together with OM produced by phytoplankton. A negative correlation between the degradation index and δ13C-POC indicates that the quality of OM significantly influences isotopic fractionation (r2 = 0.59, p < 0.001). The AA distribution in the Amundsen Sea (5.43 ± 3.19 µM) was significantly larger than previously reported in the Southern Ocean and was associated with phytoplankton biomass (r2 = 0.49, p < 0.01). Under conditions dominated by P. antarctica (DI = 2.29 ± 2.30), OM exhibited greater lability compared to conditions co-dominated by diatoms and D. speculum (DI = 0.04 ± 3.64). These results highlight the important role of P. antarctica in influencing the properties of OM, suggesting potential impacts on carbon cycling and microbial metabolic activity in the Amundsen Sea.

CREB mediates the C. elegans dauer polyphenism through direct and cell-autonomous regulation of TGF-ß expression.

Animals can adapt to dynamic environmental conditions by modulating their developmental programs. Understanding the genetic architecture and molecular mechanisms underlying developmental plasticity in response to changing environments is an important and emerging area of research. Here, we show a novel role of cAMP response element binding protein (CREB)-encoding crh-1 gene in developmental polyphenism of C. elegans. Under conditions that promote normal development in wild-type animals, crh-1 mutants inappropriately form transient pre-dauer (L2d) larvae and express the L2d marker gene. L2d formation in crh-1 mutants is specifically induced by the ascaroside pheromone ascr#5 (asc-ωC3; C3), and crh-1 functions autonomously in the ascr#5-sensing ASI neurons to inhibit L2d formation. Moreover, we find that CRH-1 directly binds upstream of the daf-7 TGF-ß locus and promotes its expression in the ASI neurons. Taken together, these results provide new insight into how animals alter their developmental programs in response to environmental changes.

Implantation of hUCB-MSCs generates greater hyaline-type cartilage than microdrilling combined with high tibial osteotomy.

PURPOSE: To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). METHODS: This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24 and 48 weeks. Secondary outcomes included arthroscopic, histological and magnetic resonance imaging assessments at 1 year. RESULTS: Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignment and clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). CONCLUSION: hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. LEVEL OF EVIDENCE: Level II, Prospective Comparative Cohort Study.

Preoperative joint line obliquity, a newly identified factor for overcorrection, can be incorporated into a novel preoperative planning method to optimise alignment in high tibial osteotomy.

PURPOSE: The aim of this study was to analyse the factors associated with additional postoperative alignment changes after accurate bony correction by selecting only patients with well-performed bony correction as planned and develop a method of incorporating significant factors into preoperative planning. METHODS: Among 104 consecutive patients who underwent medial open wedge high tibial osteotomy (MOWHTO) between October 2019 and July 2022, 61 with well-performed bony corrections were retrospectively reviewed. The major criterion for well-performed bony correction was a difference of <1° between the simulated medial proximal tibial angle (MPTA) and the actual postoperative MPTA as measured in three dimensions. Radiographic parameters, such as the joint line convergence angle (JLCA) and joint line obliquity (JLO), were measured preoperatively and postoperatively, utilising standing and supine whole lower extremity anteroposterior, valgus and varus stress radiographs. Multiple linear regression analysis identified the factors affecting alignment changes, and a prediction model was developed. A method for applying this prediction model to preoperative planning was proposed. RESULTS: Preoperative JLCA on standing (preJLCAstd ), preoperative JLCA on 0° valgus stress radiograph (vgJLCA0 ), and preoperative JLO (preJLO) were significantly correlated with JLCA change (∆JLCA) (p < 0.001, p < 0.001, p = 0.006). The prediction model was estimated as ∆JLCA = 0.493 × (vgJLCA0 ) - 0.727 × (preJLCAstd ) + 0.189 × (preJLO) - 1.587 in. (R = 0.815, modified R2 = 0.646, p < 0.001). The proposed method resulted in a reduced overcorrection rate (p = 0.003) and an improved proportion of acceptable alignments (p = 0.013). CONCLUSION: PreJLCAstd , vgJLCA0  and preJLO can be used to estimate ∆JLCA. PreJLO was recently identified as a significant factor associated with additional alignment changes. Utilising the proposed preoperative planning and a prediction model with these factors shows promise in calibrating postoperative alignment after MOWHTO. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Ibulocydine Inhibits Migration and Invasion of TNBC Cells via MMP-9 Regulation.

Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancer types, indicating a poor survival prognosis with a more aggressive biology of metastasis to the lung and a short response duration to available therapies. Ibulocydine (IB) is a novel (cyclin-dependent kinase) CDK7/9 inhibitor prodrug displaying potent anti-cancer effects against various cancer cell types. We performed in vitro and in vivo experiments to determine whether IB inhibits metastasis and eventually overcomes the poor drug response in TNBC. The result showed that IB inhibited the growth of TNBC cells by inducing caspase-mediated apoptosis and blocking metastasis by reducing MMP-9 expression in vitro. Concurrently, in vivo experiments using the metastasis model showed that IB inhibited metastasis of MDA-MB-231-Luc cells to the lung. Collectively, these results demonstrate that IB inhibited the growth of TNBC cells and blocked metastasis by regulating MMP-9 expression, suggesting a novel therapeutic agent for metastatic TNBC.

A regional-scale approach for modeling primary production and biogenic silica export in the Southern Ocean.

Persistent uncertainties in the representations of net primary production (NPP) and silicate in the Southern Ocean have been noted in recent assessments ofthe ocean biogeochemical components of Earth system models (ESMs). Consequently, more mechanistic studies at the regional scale are required. To reduce these uncertainties, we applied a one-dimensional (1D) marine ecosystem model to different bioregions in the Southern Ocean: the Polar Frontal Zone in the Pacific sector, the seasonal sea ice zone in the northwestern Ross Sea, and the inner shelf of Terra Nova Bay. To make the existing ecosystem model applicable to the Southern Ocean, we modified the phytoplankton physiology (stoichiometry depending on species) and the silicate cycle (dissolution rate of biogenic silica (BSi) depending on latitude) in the model. We quantified and compared seasonal variations in several limitation factors of NPP, namely, iron, irradiance, silicate and temperature, in the three regions. The simulation results showed that dissolved iron plays the most significant role in determining the magnitude of NPP and the phytoplankton community structure during summer. Additionally, the modified model successfully reproduced the vertical flux of BSi and particulate organic carbon (POC). The POC export efficiency was high in the inner shelf zone, which had high levels of iron concentration, NPP, and Phaeocystis biomass. In contrast, BSi export occurred most efficiently in the Polar Frontal Zone, where diatoms are dominant, the BSi dissolution rate is low, and NPP is extremely low. Our results from the integrated mechanistic framework at the regional scale demonstrate which specific processes should be urgently included in ESMs for better representation of the biogeochemical dynamics in the Southern Ocean.

Assessment of corneal and limbal epithelial thickness by spectral-domain optical coherence tomography in brachycephalic and non-brachycephalic dogs.

OBJECTIVE: To investigate the variance in corneal epithelial thickness (CET) and limbal epithelial thickness (LET) according to the age and skull type by using spectral-domain optical coherence tomography (SD-OCT) in normal dogs. ANIMALS AND PROCEDURES: This study used an eye each from 46 dogs (24 brachycephalic and 22 non-brachycephalic dogs) assessed to have clear corneas. Each dog was classified according to age into groups 1 (0-5 years), 2 (6-10 years), and 3 (>11 years). OCT imaging was performed on the central cornea for CET and perpendicular to the quadrant of the limbus for LET. The average of the maximum LET (maxLET) value was measured in four eye quadrants. RESULTS: Corneal epithelial thickness was not significantly different according to age in brachycephalic and non-brachycephalic dogs. Visualization of the limbal invagination was better when the maxLET was thick. Nasal and temporal maxLETs were significantly thicker than superior and inferior maxLETs in non-brachycephalic dogs. In brachycephalic dogs, there was a significant decrease in nasal maxLET with age (rs  = -0.489, p = .015). Significant differences between brachycephalic and non-brachycephalic dogs were observed in nasal maxLET (p = .024) and temporal maxLET (p = .011). CONCLUSIONS: Invagination was better visualized in the nasal and temporal limbal quadrants of non-brachycephalic dogs compared with brachycephalic dogs, and the maxLETs of the regions were thicker than those of the brachycephalic dogs. CET and LET measurements using SD-OCT can help in clinical assessment and research on ocular surface diseases in dogs.

EEG Parameter Selection Reflecting the Characteristics of Internet Gaming Disorder While Playing League of Legends.

Game playing is an accessible leisure activity. Recently, the World Health Organization officially included gaming disorder in the ICD-11, and studies using several bio-signals were conducted to quantitatively determine this. However, most EEG studies regarding internet gaming disorder (IGD) were conducted in the resting state, and the outcomes appeared to be too inconsistent to identify a general trend. Therefore, this study aimed to use a series of statistical processes with all the existing EEG parameters until the most effective ones to identify the difference between IGD subjects IGD and healthy subjects was determined. Thirty subjects were grouped into IGD (n = 15) and healthy (n = 15) subjects by using the Young's internet addition test (IAT) and the compulsive internet use scale (CIUS). EEG data for 16 channels were collected while the subjects played League of Legends. For the exhaustive search of parameters, 240 parameters were tested in terms of t-test, factor analysis, Pearson correlation, and finally logistic regression analysis. After a series of statistical processes, the parameters from Alpha, sensory motor rhythm (SMR), and MidBeta ranging from the Fp1, C3, C4, and O1 channels were found to be best indicators of IGD symptoms. The accuracy of diagnosis was computed as 63.5-73.1% before cross-validation. The most interesting finding of the study was the dynamics of EEG relative power in the 10-20 Hz band. This EEG crossing phenomenon between IGD and healthy subjects may explain why previous research showed inconsistent outcomes. The outcome of this study could be the referential guide for further investigation to quantitatively assess IGD symptoms.

Construction of full-length infectious clones of turnip mosaic virus isolates infecting Perilla frutescens and genetic analysis of recently emerged strains in Korea.

Perilla is an annual herb with a unique aroma and taste that has been cultivated in Korea for hundreds of years. It has been widely cultivated in many Asian and European countries as a food and medicinal crop. Recently, several viruses have been reported to cause diseases in perilla in Korea, including turnip mosaic virus (TuMV), which is known as a brassica pathogen due to its significant damage to brassica crops. In this study, we determined the complete genome sequences of two new TuMV isolates originating from perilla in Korea. Full-length infectious cDNA clones of these two isolates were constructed, and their infectivity was tested by agroinfiltration of Nicotiana benthamiana and sap inoculation of Chinese cabbage and radish plants. In addition, we analyzed the phylogenetic relationship of six new Korean TuMV isolates to members of the four major groups. We also used RDP4 software to conduct recombination analysis of recent isolates from Korea, which provided new insight into the evolutionary relationships of Korean isolates of TuMV.

Phytoplankton growth rates in the Amundsen Sea (Antarctica) during summer: The role of light.

In the Amundsen Sea, significant global warming accelerates ice melt, and is consequently altering many ocean properties such as sea ice concentration, surface freshening, water column stratification, and underwater light properties. To examine the influence of light, which is one of the fundamental factors for phytoplankton growth, incubation experiments and field surveys were performed during the austral summer of 2016. In the incubation experiments, phytoplankton abundance and carbon biomass significantly increased with increasing light levels, probably indicating light limitation. Growth rates of the small pennates (mean 0.42 d-1) increased most rapidly with an increase in light, followed by those of Phaeocystis antarctica (0.31 d-1), and the large diatoms (0.16 d-1). A short-term study during the field survey showed that phytoplankton distribution in the surface layer was likely controlled by different responses to light and the sinking rate of each species. These results suggest that the approach adopted by previous studies of explaining phytoplankton ecology as a characteristic of two major taxa, namely diatoms and P. antarctica, in the coastal Antarctic waters might cause errors owing to oversimplification and misunderstanding, since diatoms comprise several species that have different ecophysiological characteristics.

Evaluation of the upper and lower proximal lacrimal canaliculi using spectral-domain optical coherence tomography in normal Beagle dogs.

OBJECTIVE: To confirm the feasibility of visualizing upper and lower proximal lacrimal canaliculi (LC) using spectral-domain optical coherence tomography (SD-OCT). ANIMALS STUDIED: Eight eyes of four normal Beagle dogs. PROCEDURES: To obtain an upper proximal LC image, the head was turned in the opposite direction to the eye being imaged, and the medial part of the upper eyelid was everted to expose the LC. To obtain a lower LC image, the lower eyelid was everted just below the punctum. Using "angle mode", the scan line was placed parallel on the long axis of the LC. The inlet LC width (LCW) was measured. Artificial tears (AT) were instilled, and LCW was compared before and after AT instillation. Additionally, the return time to the initial LCW inlet width was recorded. RESULTS: Before AT instillation, there was a significant difference between the mean upper and lower LCW (91.8 ± 3.2 µm and 110.1 ± 8.4 µm, respectively). After AT instillation, the mean upper and lower LCW were 236.9 ± 27.7 µm and 238.4 ± 30.4 µm, respectively. Significant differences in the LCW before and after AT instillation in both the upper and lower LCWs were observed. The mean return time of the upper and lower LCW to their initial widths after AT instillation was within 4 min. CONCLUSIONS: Spectral-domain optical coherence tomography was an effective method for providing high-resolution images of the upper and lower proximal LC. This method enables observation of LC changes after instillation of eyedrops in veterinary clinical practice.

Relationship between the presence of dedicated doctors in rapid response systems and patient outcome: a multicenter retrospective cohort study.

BACKGROUND: Rapid response systems (RRSs) improve patients' safety, but the role of dedicated doctors within these systems remains controversial. We aimed to evaluate patient survival rates and differences in types of interventions performed depending on the presence of dedicated doctors in the RRS. METHODS: Patients managed by the RRSs of 9 centers in South Korea from January 1, 2016, through December 31, 2017, were included retrospectively. We used propensity score-matched analysis to balance patients according to the presence of dedicated doctors in the RRS. The primary outcome was in-hospital survival. The secondary outcomes were the incidence of interventions performed. A sensitivity analysis was performed with the subgroup of patients diagnosed with sepsis or septic shock. RESULTS: After propensity score matching, 2981 patients were included per group according to the presence of dedicated doctors in the RRS. The presence of the dedicated doctors was not associated with patients' overall likelihood of survival (hazard ratio for death 1.05, 95% confidence interval [CI] 0.93‒1.20). Interventions, such as arterial line insertion (odds ratio [OR] 25.33, 95% CI 15.12‒42.44) and kidney replacement therapy (OR 10.77, 95% CI 6.10‒19.01), were more commonly performed for patients detected using RRS with dedicated doctors. The presence of dedicated doctors in the RRS was associated with better survival of patients with sepsis or septic shock (hazard ratio for death 0.62, 95% CI 0.39‒0.98) and lower intensive care unit admission rates (OR 0.53, 95% CI 0.37‒0.75). CONCLUSIONS: The presence of dedicated doctors within the RRS was not associated with better survival in the overall population but with better survival and lower intensive care unit admission rates for patients with sepsis or septic shock.

The association between hospital length of stay before rapid response system activation and clinical outcomes: a retrospective multicenter cohort study.

BACKGROUND: Rapid response system (RRS) is being increasingly adopted to improve patient safety in hospitals worldwide. However, predictors of survival outcome after RRS activation because of unexpected clinical deterioration are not well defined. We investigated whether hospital length of stay (LOS) before RRS activation can predict the clinical outcomes. METHODS: Using a nationwide multicenter RRS database, we identified patients for whom RRS was activated during hospitalization at 9 tertiary referral hospitals in South Korea between January 1, 2016, and December 31, 2017. All information on patient characteristics, RRS activation, and clinical outcomes were retrospectively collected by reviewing patient medical records at each center. Patients were categorized into two groups according to their hospital LOS before RRS activation: early deterioration (LOS < 5 days) and late deterioration (LOS ≥ 5 days). The primary outcome was 28-day mortality and multivariable logistic regression was used to compare the two groups. In addition, propensity score-matched analysis was used to minimize the effects of confounding factors. RESULTS: Among 11,612 patients, 5779 and 5883 patients belonged to the early and late deterioration groups, respectively. Patients in the late deterioration group were more likely to have malignant disease and to be more severely ill at the time of RRS activation. After adjusting for confounding factors, the late deterioration group had higher 28-day mortality (aOR 1.60, 95% CI 1.44-1.77). Other clinical outcomes (in-hospital mortality and hospital LOS after RRS activation) were worse in the late deterioration group as well, and similar results were found in the propensity score-matched analysis (aOR for 28-day mortality 1.66, 95% CI 1.45-1.91). CONCLUSIONS: Patients who stayed longer in the hospital before RRS activation had worse clinical outcomes. During the RRS team review of patients, hospital LOS before RRS activation should be considered as a predictor of future outcome.

Methods to generate site-specific conjugates of antibody and protein.

Antibody-protein conjugates have been useful tools for studying biological systems and also played important roles in developing therapeutics and diagnostics. In particular, because of the increased interest in therapeutics of complexity higher than monoclonal antibodies, various methods have been reported for generating bispecific antibodies, immunotoxins, and antibody-enzyme conjugates in which antibodies are site-specifically conjugated with other proteins. Compared with conjugating antibodies with synthetic molecules, controlling the modification sites is difficult in the antibodies conjugated with protein cargos due to the presence of several reactive groups in both molecules. Enzymatic reactions are often used to generate antibody-protein conjugates owing to their high specificity for both reactants and products. Chemical modifications involving genetic introduction of natural or unnatural amino acid residues have also been used for site-specific conjugation of antibodies. Recent studies have developed methods to modify native antibodies using peptides having affinity for antibodies, and these methods do not need antibody engineering for conjugation reactions. In this review, we have summarized enzymatic and chemical approaches to generate site-specific antibody-protein conjugates.

Rapid Response System Should Be Enhanced at Non-general Ward Locations: a Retrospective Multicenter Cohort Study in Korea.

BACKGROUND: A rapid response system (RRS) contributes to the safety of hospitalized patients. Clinical deterioration may occur in the general ward (GW) or in non-GW locations such as radiology or dialysis units. However, there are few studies regarding RRS activation in non-GW locations. This study aimed to compare the clinical characteristics and outcomes of patients with RRS activation in non-GW locations and in the GW. METHODS: From January 2016 to December 2017, all patients requiring RRS activation in nine South Korean hospitals were retrospectively enrolled and classified according to RRS activation location: GW vs non-GW RRS activations. RESULTS: In total, 12,793 patients were enrolled; 222 (1.7%) were non-GW RRS activations. There were more instances of shock (11.6% vs. 18.5%) and cardiac arrest (2.7% vs. 22.5%) in non-GW RRS activation patients. These patients also had a lower oxygen saturation (92.6% ± 8.6% vs. 88.7% ± 14.3%, P < 0.001) and a higher National Early Warning Score 2 (7.5 ± 3.4 vs. 8.9 ± 3.8, P < 0.001) than GW RRS activation patients. Although non-GW RRS activation patients received more intubation (odds ratio [OR], 3.135; P < 0.001), advanced cardiovascular life support (OR, 3.912; P < 0.001), and intensive care unit transfer (OR, 2.502; P < 0.001), their hospital mortality (hazard ratio, 0.630; P = 0.013) was lower than GW RRS activation patients upon multivariate analysis. CONCLUSION: Considering that there were more critically ill but recoverable cases in non-GW locations, active RRS involvement should be required in such locations.

Could DOAC Be a Better Choice Than Warfarin in Low Compliance Patients with Fontan Procedure?

Background and Objectives: After the Fontan procedure, thromboembolic events need to be prevented. We present a young patient with a history of Fontan procedure and poor adherence to warfarin who developed systemic thromboembolism. He was changed to maintenance dabigatran, which is one of the available direct oral anticoagulants (DOACs). Case presentation: A 20-year-old man was diagnosed with cerebral infarct, pulmonary thromboembolism (PTE), and renal infarcts. He was prescribed warfarin to prevent thromboembolic events after the Fontan procedure. Based on his poor adherence to warfarin, we decided to change the anticoagulant therapy from warfarin to dabigatran 150 mg bid. One month later, his pulmonary thromboembolism regressed. Conclusion: Our case report showed a young adult with low compliance to warfarin who developed cerebral, pulmonary, and renal thromboembolic events. Thus, in our opinion, the change from warfarin to a DOAC was necessary for further prevention and treatment of PTE. A change from warfarin to a DOAC should be considered in patients with poor compliance who are at high risk of thromboembolic events, for example, after the Fontan procedure.

FCHO1560-571 peptide, a PKB kinase motif, inhibits tumor progression.

BACKGROUND: Cell division is regulated by protein kinase B (PKB)-mediated FCH domain only 1 (FCHO1) phosphorylation. METHODS: FCHO1560-571, a synthetic water-soluble peptide, was generated from the PKB substrate motif 560PPRRLRSRKVSC571 found in the human FCHO1 protein. RESULTS: In this study, we found that in vitro FCHO1560-571 inhibits cell proliferation via PKB/ERK/SMAD4 pathways in KRAS-mutated A549 lung cancer cells. In addition, FCHO1560-571, at effective doses of 15 and 30 mg/kg, significantly suppressed tumor growth and decreased the size and weight of tumors in A549-xenograft mice. CONCLUSION: These results suggest that the FCHO1560-571 peptide could be a potential therapy for lung cancer.