Cullin-RING E3 ubiquitin ligase 4 regulates neurite morphogenesis during neurodevelopment.

Neuritogenesis is crucial for establishing proper neuronal connections during brain development; its failure causes neurodevelopmental defects. Cullin-RING E3 ubiquitin ligase complexes participate in various neurodevelopmental processes by regulating protein stability. We demonstrated the regulatory function of Cullin-RING E3 ubiquitin ligase 4 (CRL4) in neurite morphogenesis during early neurodevelopment. Cul4a and Cul4b, the core scaffold proteins of CRL4, exhibit high expression and activation within the cytosol of developing neurons, regulated by neuronal stimulation through N-methyl D-aspartate (NMDA) receptor signaling. CRL4 also interacts with cytoskeleton-regulating proteins involved in neurite morphogenesis. Notably, genetic depletion and inhibition of cytosolic CRL4 enhance neurite extension and branching in developing neurons. Conversely, Cul4a overexpression suppresses basal and NMDA-enhanced neuritogenesis. Furthermore, CRL4 and its substrate adaptor regulate the polyubiquitination and proteasomal degradation of doublecortin protein. Collectively, our findings suggest that CRL4 ensures proper neurite morphogenesis in developing neurons by regulating cytoskeleton-regulating proteins.

The unequal landscape of civic opportunity in America.

The hollowing of civil society has threatened effective implementation of scientific solutions to pressing public challenges-which often depend on cultivating pro-social orientations commonly studied under the broad umbrella of social capital. Although robust research has studied the constituent components of social capital from the demand side (that is, the orientations people need for collective life in pluralistic societies, such as trust, cohesion and connectedness), the same precision has not been brought to the supply side. Here we define the concept of civic opportunity-opportunities people have to encounter civic experiences necessary for developing such orientations-and harness data science to map it across America. We demonstrate that civic opportunity is more highly correlated with pro-social outcomes such as mutual aid than other measures, but is unequally distributed, and its sources are underrepresented in the public dialogue. Our findings suggest greater attention to this fundamentally uneven landscape of civic opportunity.

Changes in Lower Extremity Muscle Quantity and Quality in Patients with Subacute Stroke.

OBJECTIVE: To analyze the changes in muscle mass and quality with time on the paretic and non-paretic sides in subacute stroke patients and identify correlations between the variation of muscle mass and quality and lower limb functions. METHODS: Thirty hemiplegia patients diagnosed with stroke participated in this study. To evaluate poststroke muscle changes, longitudinal measurement of muscle mass and quality was conducted with bilateral lower limbs. The elastic shear modulus was measured using shear wave elastography and muscle thickness (MT) of rectus femoris, vastus intermedius, vastus lateralis (VL), vastus medialis, tibialis anterior, and gastrocnemius (GCM) muscles. Functional evaluation was performed using Berg Balance Scale (BBS), Five Times Sit to Stand Test (FTSST). Follow-up was performed at discharge. The muscle mass and quality were compared according to time. We analyzed whether muscle quantity and quality were related to function. RESULTS: MT demonstrated no significant change with time. The elastic shear modulus increased significantly in the paretic VL and GCM muscles and did not change significantly in the muscles on the non-paretic side. Correlation analysis detected that elastic shear modulus in the VL has a cross-sectional negative relationship between BBS and positive relationship between FTSST. There were significant correlation between variation of FTSST and the variation of the elastic shear modulus in VL. CONCLUSION: Only paretic VL and GCM muscle quality changed in subacute stroke patients and muscle's property related to lower limb functions. Therefore, the lower extremity requires an approach to muscle quality rather than quantity for subacute stroke patients.

Aminoalcohol derivatives by nickel-catalyzed enantioselective coupling of imines and dienol ethers.

The reductive coupling of dienol ethers with N-tosylimines catalyzed by Ni(0) in the presence of a VAPOL-derived phosphoramidite ligand follows an unprecedented regiochemical course; it furnishes syn-configured 1,2-aminoalcohol derivatives in good chemical yields with up to 94% ee.

How to avoid prostate biopsy in men with Prostate Image-Reporting and Data System 3 lesion? Development and external validation of new biopsy indication using prostate health index density.

Background: To develop a customized prostate biopsy indication using prostate health index density (PHID) combined with multiparametric magnetic resonance imaging (mpMRI) and assess the reliability of the PHID cutoff value in external populations. Methods: A total of 521 cognitive MRI/ultrasonography fusion prostate biopsies and biomarker tests for prostate-specific antigen (PSA), free PSA, and PHI were performed after mpMRI. The predictive value for clinically significant prostate cancer (csPCa; Gleason score≥7) of PSA derivatives was examined using the ROC curve. We developed a new biopsy indication utilizing a PHID cutoff based on the Prostate Image-Reporting and Data System (PI-RADS) score, which was externally validated. Results: The combination of PHID and mpMRI (AUC = 0.884) demonstrated the highest predictive ability for csPCa, although PHID (AUC = 0.843) and PI-RADS (AUC = 0.806) individually also showed a high diagnostic value. When a PHID cutoff of 0.75 was used in men with PI-RADS 3 lesions, the negative predictive value of csPCa was 100%, and approximately half of the biopsies could be safely avoided. Conclusion: Compared to PHID or PI-RADS scores alone, the combination of PHID and PI-RADS scores increased the accuracy of csPCa detection and the number of cases in which biopsy could be avoided. In men with PI-RADS 3 lesions, the optimal PHID cutoff ≥0.75 can prevent half of the unnecessary biopsies without missing csPCa. In men with PI-RADS 4-5 lesions, biopsies are warranted regardless of PHID values because csPCa could be accompanied by low PHID.

Epidemiologic and Clinical Characteristics of Patients with Severe Fever with Thrombocytopenia Syndrome at Tertiary Hospital in Jeju for 10 years.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), which was first discovered in China in 2009, is an infectious disease with a high mortality rate, particularly in East Asia. This study aimed to investigate the epidemiological and clinical characteristics and risk factors for mortality by analyzing SFTS cases accumulated for up to ten years in Jeju, Korea. MATERIALS AND METHODS: Medical records of patients diagnosed with SFTS between March 2013 and August 2022 at a tertiary hospital in Jeju were analyzed retrospectively. We investigated data of patients with SFTS on the epidemiologic and clinical characteristics, laboratory findings, and administered treatments and compared the differences between fatal and non-fatal groups. RESULTS: We enrolled 91 SFTS-confirmed patients. The median age of patients was 62 years, and the fatality rate increased with age (P = 0.004). Fever was the most common symptom (84.6%), and diarrhea (37.4%) was also present in some cases. The overall fatality rate was 10.9%. Dyspnea (20.0% vs. 0.0%, P = 0.009) and changes in mental status (70.0% vs. 11.0%, P <0.001) were more frequent in fatal cases. Risk factor assessment revealed that a high aspartate aminotransferase /alanine aminotransferase ratio (odds ratio [OR]: 39.568, 95% confidence interval [CI]: 1.479 - 1,058.639, P = 0.028) and elevated total bilirubin levels (OR: 53.037, 95% CI: 1.064 - 2,643.142, P = 0.046) were also significantly associated with fatal cases. Plasma exchange (40.7%) was the most commonly administered treatment. CONCLUSION: SFTS has a high mortality rate; therefore, awareness of SFTS must be raised among physicians and citizens living in tick-inhabited areas, such as Jeju.

Incidence and risk factors for pressure injury in hospitalized non-small cell lung cancer patients: A retrospective observational study.

AIM: This study aimed to identify the incidence and risk factors for pressure injury in patients hospitalized for non-small cell lung cancer (NSCLC). METHODS: This retrospective observational study was conducted in 645 adults who were hospitalized for NSCLC. Clinicopathological characteristics were compared between NSCLC patients with pressure injury and those without pressure injury. RESULTS: Among total 645 patients, 180 patients showed pressure injury with an incidence of 27.9%. Patients with pressure injury showed increased serum C-reactive protein (CRP) levels (P < 0.001), increased neutrophil-lymphocyte ratio (P = 0.002), and increased platelet-lymphocyte ratio (P = 0.001) more often. Increase in serum CRP levels at the time of admission was the major risk factor for development of pressure injury in NSCLC patients (OR = 2.20; 95% CI [1.40-3.45]; P = 0.001). Also, among major inflammatory markers, serum CRP levels at the time of admission showed weak negative correlation with the period from admission to the development of pressure injury (r = -0.216, P = 0.004). CONCLUSION: By checking serum CRP levels at the time of admission, the NSCLC patients at high risk for the development of pressure injury can be identified in advance and the occurrence of pressure injury can be reduced by applying more active preventive nursing care. CLINICAL TRIAL REGISTRATION NUMBER: KCT0006570.

Developing and Establishing a Wound Dressing Team: Experience and Recommendations.

BACKGROUND: The existing literature has comprehensively examined the benefits of specialized wound-care services and multidisciplinary team care. However, information on the development and integration of wound-dressing teams for patients who do not require specialized wound care is scarce. Therefore, the present study aimed to elucidate the benefits of a wound-dressing team by reporting our experiences with the establishment of a wound-dressing team. METHODS: The wound-dressing team was established at Korea University Guro Hospital. Between July 2018 and June 2022, 180,872 cases were managed for wounds at the wound-dressing team. The data were analyzed to assess the types of wounds and their outcomes. In addition, questionnaires assessing the satisfaction with the service were administered to patients, ward nurses, residents/internists, and team members. RESULTS: Regarding the wound type, 80,297 (45.3%) were catheter-related, while 48,036 (27.1%), 26,056 (14.7%), and 20,739 (11.7%) were pressure ulcers, dirty wounds, and simple wounds, respectively. In the satisfaction survey, the scores of the patient, ward nurse, dressing team nurse, and physician groups were 8.9, 8.1, 8.2, and 9.1, respectively. Additionally, 136 dressing-related complications (0.08%) were reported. CONCLUSION: The wound dressing team can enhance satisfaction among patients and healthcare providers with low complications. Our findings may provide a potential framework for establishing similar service models.

Increased PRL-1 in BM-derived MSCs triggers anaerobic metabolism via mitochondria in a cholestatic rat model.

Mesenchymal stem cell (MSC) therapy in chronic liver disease is associated with mitochondrial anaerobic metabolism. Phosphatase of regenerating liver-1 (PRL-1), known as protein tyrosine phosphatase type 4A, member 1 (PTP4A1), plays a critical role in liver regeneration. However, its therapeutic mechanism remains obscure. The aim of this study was to establish genetically modified bone marrow (BM)-MSCs overexpressing PRL-1 (BM-MSCsPRL-1) and to investigate their therapeutic effects on mitochondrial anaerobic metabolism in a bile duct ligation (BDL)-injured cholestatic rat model. BM-MSCsPRL-1 were generated with lentiviral and nonviral gene delivery systems and characterized. Compared with naive cells, BM-MSCsPRL-1 showed an improved antioxidant capacity and mitochondrial dynamics and decreased cellular senescence. In particular, mitochondrial respiration in BM-MSCsPRL-1 generated using the nonviral system was significantly increased as well as mtDNA copy number and total ATP production. Moreover, transplantation of BM-MSCsPRL-1 generated using the nonviral system had predominantly antifibrotic effects and restored hepatic function in a BDL rat model. Decreased cytoplasmic lactate and increased mitochondrial lactate upon the administration of BM-MSCsPRL-1 indicated significant alterations in mtDNA copy number and ATP production, activating anaerobic metabolism. In conclusion, BM-MSCsPRL-1 generated by a nonviral gene delivery system enhanced anaerobic mitochondrial metabolism in a cholestatic rat model, improving hepatic function.

Validated names for experimental studies on race and ethnicity.

A large and fast-growing number of studies across the social sciences use experiments to better understand the role of race in human interactions, particularly in the American context. Researchers often use names to signal the race of individuals portrayed in these experiments. However, those names might also signal other attributes, such as socioeconomic status (e.g., education and income) and citizenship. If they do, researchers would benefit greatly from pre-tested names with data on perceptions of these attributes; such data would permit researchers to draw correct inferences about the causal effect of race in their experiments. In this paper, we provide the largest dataset of validated name perceptions to date based on three different surveys conducted in the United States. In total, our data include over 44,170 name evaluations from 4,026 respondents for 600 names. In addition to respondent perceptions of race, income, education, and citizenship from names, our data also include respondent characteristics. Our data will be broadly helpful for researchers conducting experiments on the manifold ways in which race shapes American life.

Metachronous Contralateral Occurrence of Hydrocele After Unilateral Hydrocelectomy in Children Younger Than 8 Years.

BACKGROUND: Hydrocele on the contralateral side after surgical repair is an uncommon condition compared to surgical site recurrence. Although there has been much research on metachronous contralateral inguinal hernia in children, metachronous contralateral hydrocele, which share a common pathology with inguinal hernias, has not yet been investigated. We have investigated the incidence and risk factors for metachronous contralateral occurrence of communicating and noncommunicating hydroceles in children younger than 8 years. METHODS: From January 2017 to June 2020, 302 children younger than 8 who were diagnosed with unilateral hydroceles were treated in our hospital without surgical exploration of contralateral hydrocele. The disease was classified into communicating and noncommunicating hydroceles. We divided patients into two groups according to the presence of metachronous contralateral hydrocele and analyzed the differences between the two groups. RESULTS: Among 302 patients, the mean age was 36.4 ± 20.9 months. Metachronous contralateral hydrocele occurred in 15 (4.9%) patients as communicating hydroceles. Comparison between the two groups showed statistically significant differences in type of hydrocele (P = 0.047) at first diagnosis. CONCLUSION: Clinically evident risk of metachronous contralateral hydrocele after unilateral hydrocelectomy was 4.9%. Despite the relatively low incidence rate, the risk of metachronous contralateral occurrence should always be consulted with parents before surgical treatment of hydroceles.

Enhanced delivery of the phototherapeutic nanoparticles via hepatocyte overload.

Phototherapeutic nanoparticles (NPs) were prepared with methylene blue (MB), indocyanine green (ICG), and Solutol through self-assembly. Generation of reactive oxygen species and elevation of temperature were observed that verify the photodynamic/photothermal effects of the NPs. Morphology and size distribution of the NPs were examined by transmittance electron microscopy and dynamic light scattering. The biodistribution of the NPs and their antitumor efficacy were examined using tumor-bearing mice to understand the phototherapeutic effect of the NPs on tumors. To enhance targetability with enhanced therapeutic efficacy, empty NPs (Solutol nanoparticles without MB and ICG) at different concentrations were injected along with the phototherapeutic NPs. Enhanced delivery of the phototherapeutic NPs at the tumor site was examined based on hepatocyte overload.

The Impact of the Percent of Residual Prostate-Specific Antigen on Metastasis-Free Survival in Patients with Persistent Prostate-Specific Antigen after Radical Prostatectomy.

PURPOSE: Persistent levels of prostate-specific antigen (PSA) is a poor prognostic factor for recurrence after radical prostatectomy (RP). We investigated the impact of the percentage of residual PSA (%rPSA) [(post-/preoperative PSA)×100], representing a biochemical residual tumor, and the first postoperative PSA (fPSA) level on metastasis-free survival (MFS) in men with persistent levels of PSA after RP. MATERIALS AND METHODS: We retrospectively identified male patients within a single tertiary referral hospital database who harbored persistent (≥0.1 ng/mL) vs. undetectable (<0.1 ng/mL) PSA levels 4 to 8 weeks after RP. Kaplan-Meier analyses and Cox regression models were used to test the effect of persistent PSA levels, the fPSA level, and %rPSA on MFS. RESULTS: Of 1,205 patients, 178 patients with persistent PSA levels were enrolled. Seven-year MFS rates were 60.5% vs. 84.3% (p<0.001) for patients with a %rPSA ≥6% and <6%, respectively. Multivariable Cox regression models of the overall cohort revealed that persistent PSA levels (hazard ratio [HR], 3.94; p=0.010), extracapsular extension (HR, 4.17; 95% confidence interval [CI], 1.06-16.41; p=0.041), and pathological Gleason grade group (pGGG) (HR, 3.69; 95% CI, 1.32-10.27; p=0.013) were independent predictors of metastasis. Multivariable Cox regression models in men with persistent PSA levels revealed that the %rPSA (HR, 8.92; 95% CI, 1.74-45.71; p=0.009) and pGGG 4-5 (HR, 4.13; 95% CI, 1.22-13.96; p=0.022) were independent predictors of distant metastasis, but not the fPSA level after surgery. CONCLUSIONS: Persistent levels of PSA were associated with worse MFS after RP. In men with persistent PSA levels after RP, the %rPSA is a valuable predictor of MFS unlike the fPSA level.

Nickel-Catalyzed Enantioselective Coupling of Aldehydes and Electron-Deficient 1,3-Dienes Following an Inverse Regiochemical Course.

The nickel catalyzed reductive coupling of aldehydes with sorbate esters and related electron-deficient 1,3-dienes are known in the literature to occur at the π-bond proximal to the ester to afford aldol-type products. In stark contrast to this established path, a VAPOL-derived phosphoramidite ligand in combination with a bench-stable nickel precatalyst brokers a regiocomplementary course in that C-C bond formation proceeds exclusively at the distal alkene site to give deoxypropionate type products carrying an acrylate handle; they can be made in either anti- or syn-configured form. In addition to this enabling reverse pathway, the reaction is distinguished by excellent levels of chemo-, diastereo-, and enantioselectivity; moreover, it can be extended to the catalytic formation of F3C-substituted stereogenic centers. The use of a dienyl pinacolboronate instead of a sorbate ester is also possible, which opens access to valuable chiral borylated building blocks in optically active form.

External validation of European Association of Urology NMIBC risk scores to predict progression after transurethral resection of bladder tumor in Korean patients with non-muscle-invasive bladder cancer.

PURPOSE: This study aimed to validate the newly proposed risk model in Korean patients diagnosed with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A retrospective review was performed with 1,238 patients who underwent transurethral resection of bladder tumor from 2009 to 2020. We included 973 patients and categorized them into four risk groups according to the European Association of Urology (EAU) NMIBC risk stratification standards, which incorporate the World Health Organization 2004/2016 grading classification. Kaplan-Meyer survival analysis and multivariable analysis of time to progression were performed to calculate the probability of progression for all risk groups. RESULTS: A total of 973 patients were followed for 54.85 months. Patients were classified according to the risk factors proposed by the new NMIBC risk table and stratified into low, intermediate, high, and very high-risk groups based on the table. Cancer progression into muscle-invasive bladder cancer (MIBC) in each risk group was observed in 7 (4.4%), 24 (15.2%), 76 (48.1%), and 51 (32.3%) individuals, respectively. The progression rate was distinguishable between risk groups in the Kaplan-Meier progression-free survival analysis, and higher risk was associated with a higher rate of progression. The new NMIBC risk variables were demonstrated to have prognostic value in the multivariate analysis. The very high-risk group was associated with progression to muscle-invasive disease. CONCLUSIONS: This study demonstrates that the new EAU NMIBC risk group categorization is feasible in predicting the progression of NMIBC into MIBC in the Korean population and thus should be applied to clinical practice in Korea.

Influence of Mechanical Fatigue at Different States of Charge on Pouch-Type Li-Ion Batteries.

Since flexible devices are being used in various states of charge (SoCs), it is important to investigate SoCs that are durable against external mechanical deformations. In this study, the effects of a mechanical fatigue test under various initial SoCs of batteries were investigated. More specifically, ultrathin pouch-type Li-ion polymer batteries with different initial SoCs were subjected to repeated torsional stress and then galvanostatically cycled 200 times. The cycle performance of the cells after the mechanical test was compared to investigate the effect of the initial SoCs. Electrochemical impedance spectroscopy was employed to analyze the interfacial resistance changes of the anode and cathode in the cycled cells. When the initial SoC was at 70% before mechanical deformation, both electrodes well maintained their initial state during the mechanical fatigue test and the cell capacity was well retained during the cycling test. This indicates that the cells could well endure mechanical fatigue stress when both electrodes had moderate lithiation states. With initial SoCs at 0% and 100%, the batteries subjected to the mechanical test exhibited relatively drastic capacity fading. This indicates that the cells are vulnerable to mechanical fatigue stress when both electrodes have high lithiation states. Furthermore, it is noted that the stress accumulated inside the batteries caused by mechanical fatigue can act as an accelerated degradation factor during cycling.

Visible Light-Mediated Enantioselective Addition of α-Aminoalkyl Radicals to Ketones Catalyzed by Chiral Oxazaborolidinium Ion.

The development of a visible light-mediated synthetic method for chiral 1,2-amino tertiary alcohols is described. In the presence of a chiral oxazaborolidinium ion catalyst and photosensitizer, the enantioselective addition of an α-aminoalkyl radical to aryl methyl ketones under visible light provides chiral 1,2-amino tertiary alcohol derivatives in high yields (up to 88%) with excellent enantioselectivities (up to 98% ee). With mechanistic studies such as radical trapping analysis, radical clock analysis, and the measurement of quantum yield, a plausible catalytic cycle is proposed.

Reset First Resistive Switching in Ni1-xO Thin Films as Charge Transfer Insulator Deposited by Reactive RF Magnetron Sputtering.

Reset-first resistive random access memory (RRAM) devices were demonstrated for off-stoichiometric Ni1-xO thin films deposited using reactive sputtering with a high oxygen partial pressure. The Ni1-xO based RRAM devices exhibited both unipolar and bipolar resistive switching characteristics without an electroforming step. Auger electron spectroscopy showed nickel deficiency in the Ni1-xO films, and X-ray photoemission spectroscopy showed that the Ni3+ valence state in the Ni1-xO films increased with increasing oxygen partial pressure. Conductive atomic force microscopy showed that the conductivity of the Ni1-xO films increased with increasing oxygen partial pressure during deposition, possibly contributing to the reset-first switching of the Ni1-xO films.