Real-world safety and effectiveness of lenvatinib in unresectable hepatocellular carcinoma in Korea: post-marketing study.

Aim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea.Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea.Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n = 511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration (p < 0.001).Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea.Clinical trial registration: ClinicalTrials.gov NCT05225207.

[Box: see text].

Proximal Location of Optic Disc Hemorrhage and Glaucoma Progression.

Importance: Although optic disc hemorrhage (DH) is widely recognized as a glaucoma risk factor, its clinical relevance in relation to proximity has not been investigated. Objective: To determine the association of the proximal location of DH with glaucoma progression. Design, Setting, and Participants: In this longitudinal observational cohort study, 146 eyes of 146 patients at Seoul National University Hospital who had had 1 or more DH with at least 5 years of follow-up and had at least 5 reliable visual field examinations were included. These data were analyzed January 10, 2010, through June 27, 2017. Exposures: Laminar, marginal, rim, and parapapillary subtypes of DH were identified based on their respective proximal locations. The laminar and marginal subtypes were classified into the cup-type group, while the rim and parapapillary subtypes were classified into the peripapillary-type group. Kaplan-Meier survival analysis was used to compare survival experiences and multivariate analysis with the Cox proportional hazard model to identify risk factors for glaucoma progression. Regression analyses, both univariate and multivariate, were used to discover significant indicators of mean deviation (MD) loss. Main Outcome and Measure: The primary outcome was glaucoma progression. Glaucoma progression was defined either as structural or functional deterioration. Results: For all of the eyes, the mean follow-up period was 10.9 (3.7) years (range, 5.1-17.8 years), the mean age at which DH was first detected was 55.1 (11.3) years (range, 21-77 years), and 94 participants were female (64.1%). Over the mean follow-up period of 10.9 years, glaucoma progression was detected in 94 eyes (61.4%) with an MD change of -0.48 dB per year. The cup-type group showed a faster rate of MD change relative to the peripapillary-type group (-0.56 vs -0.32 dB per year; difference = -0.24; 95% CI, -0.37 to -0.11; P = .01). The cup group showed a higher cumulative probability of progression of glaucoma (80.4%) relative to the peripapillary group (54.4%; difference = 26.0%; 95% CI, 11.4%-40.6%; P < .001) in a life table analysis. The presence of cup hemorrhage was associated with an increased risk of glaucoma progression (hazard ratio, 3.28; 95% CI, 2.12-5.07; P < .001) in the multivariate Cox proportional hazard model. Cup-type DH was associated to MD loss rate in regression analysis. Conclusions And Relevance: This study showed glaucoma progression was higher in cases of DH classified as the cup type. These findings support the potential utility of assessing the proximal location of DH to predict how glaucoma might progress.

Comparison of three HPLC analytical methods: ELSD, RID, and UVD for the analysis of xylitol in foods.

In this study, xylitol, a common sweetener and sucrose substitute in low-calorie foods, was quantified by high-performance liquid chromatography (HPLC). During the establishment of the analytical method, three representative detection approaches, ultraviolet detector (UVD), evaporative light scattering detector, and refractive index detector, were compared and applied to determine the xylitol content in various foods distributed in Korea. The results were compared for method validation, measurement uncertainty, and applicability. As a result, HPLC-UVD showed the lowest limit of detection (0.01 mg/L) and limit of quantification (0.04 mg/L) among the three methods. It showed a low range of relative expanded uncertainty (1.12-3.98%) and could quantify xylitol in the wide range of the samples, even trace amounts of xylitol. Therefore, a total of 160 food items, including chewing gum, candy, beverage, tea, other processed products, and beverage base, were applied with three replicates by the proposed HPLC-UVD method.

Baseline Viral Load and On-treatment Hepatocellular Carcinoma Risk in Chronic Hepatitis B: A Multinational Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) risk persists in patients with chronic hepatitis B (CHB) despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain. METHODS: This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable. RESULTS: In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared with those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk. CONCLUSION: Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic patients with CHB. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in patients with CHB.

Validation, measurement uncertainty, and determination of polysorbate-labeled foods distributed in Korea.

This study reports the improvement and validation of a colorimetric method to quantify polysorbates (20, 60, 65, and 80) in food by measuring absorbance at 620 nm using ultraviolet-visible spectrophotometry. The method was validated for linearity, limit of detection (LOD), limit of quantitation (LOQ), precision, accuracy, and measurement uncertainty. The coefficient of determination was linear (r 2 ≥ 0.9991) over the measured concentration range of 50-1000 mg/L. The LOD and LOQ were 2.3-4.9 and 7.0-15.0 mg/kg, respectively. Intra-day and inter-day accuracy and precision were 91.9-104.1% and 0.1-1.1% RSD, and 91.6-103.8% and 0.4-5.0% RSD, respectively. The result of inter-laboratory recovery was 90.9-99.8% and the measurement uncertainty was < 16% with the compliance of the CODEX recommendation. Sauce, bread, whipped cream, rice cake, ice cream, and various other polysorbate-labeled food products (n = 229, detection range; N.D.-16,442.3 mg/kg) distributed in Korea were analyzed to confirm the applicability of the analytical method. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01544-w.

Long-Term Outcomes of Gamma Knife Radiosurgery for Cerebral Cavernous Malformations: 10 Years and Beyond.

BACKGROUND: We aimed to evaluate long-term outcomes of gamma knife radiosurgery (GKS) for cerebral cavernous malformations (CCMs). METHODS: Among the 233 CCM patients who underwent GKS, 79 adult patients (96 lesions) followed for over 10 years were included and analyzed retrospectively. Annual hemorrhage rate (AHR) was analyzed the entire cohort of 233 patients and the subset of 79 enrolled patients by dividing lesions into overall CCM lesions and brainstem lesions. AHR, neurologic outcome, adverse radiation effect (ARE), and changes of lesions in magnetic resonance imaging (MRI) were compared before and after GKS. Cox-regression analysis was performed to identify risk factors for hemorrhage following GKS. RESULTS: Mean follow-up duration of 79 enrolled patients was 14 years (range, 10-23 years). The AHR of all CCMs for entire cohort at each time point was 17.8% (pre-GKS), 5.9% (≤ 2 years post-GKS), 1.8% (≤ 10 years post-GKS). The AHR of all CCM for 79 enrolled patients was 21.4% (pre-GKS), 3.8% (2 years post-GKS), 1.4% (10 years post-GKS), and 2.3% (> 10 years post-GKS). The AHR of brainstem cavernous malformation (CM) for entire cohort at each time point was 22.4% (pre-GKS), 10.1% (≤ 2 years post-GKS), 3.2% (≤ 10 years post-GKS). The AHR of brainstem CM for 79 enrolled patients was 27.2% (pre-GKS), 5.8% (2 years post-GKS), 3.4% (10 years post-GKS), and 3.5% (> 10 years post-GKS). Out of the 79 enrolled patients, 35 presented with focal neurologic deficits at the initial clinical visit. Among these patients, 74.3% showed recovery at the last follow-up. Symptomatic ARE occurred in five (6.4%) patients. No mortality occurred. Most lesions were decreased in size at the last follow-up MRI. Previous hemorrhage history (hazard ratio [HR], 8.38; 95% confidence interval [CI], 1.07-65.88; P = 0.043), and brainstem location (HR, 3.10; 95% CI, 1.26-7.64; P = 0.014) were significant risk factors for hemorrhage event. CONCLUSION: GKS for CCM showed favorable long-term outcomes. GKS should be considered for CCM, especially when it has a previous hemorrhage history and brainstem location.

Detecting microsatellite instability by length comparison of microsatellites in the 3' untranslated region with RNA-seq.

Microsatellite instability (MSI), a phenomenon caused by deoxyribonucleic acid (DNA) mismatch repair system deficiencies, is an important biomarker in cancer research and clinical diagnostics. MSI detection often involves next-generation sequencing data, with many studies focusing on DNA. Here, we introduce a novel approach by measuring microsatellite lengths directly from ribonucleic acid sequencing (RNA-seq) data and comparing its distribution to detect MSI. Our findings reveal distinct instability patterns between MSI-high (MSI-H) and microsatellite stable samples, indicating the efficacy of RNA-based MSI detection. Additionally, microsatellites in the 3'-untranslated regions showed the greatest predictive value for MSI detection. Notably, this efficacy extends to detecting MSI-H samples even in tumors not commonly associated with MSI. Our approach highlights the utility of RNA-seq data in MSI detection, facilitating more precise diagnostics through the integration of various biological data.

Chromatin remodeling-driven autophagy activation induces cisplatin resistance in oral squamous cell carcinoma.

It is still challenging to predict the efficacy of cisplatin-based therapy, particularly in relation to the activation of macroautophagy/autophagy in oral squamous cell carcinoma (OSCC). We studied the effect of selected chromatin remodeling genes on the cisplatin resistance and their interplay with autophagy in 3-dimensional tumor model and xenografts. We analyzed gene expression patterns in the cisplatin-sensitive UMSCC1, and a paired cisplatin-resistant UM-Cis cells. Many histone protein gene clusters involved in nucleosome assembly showed significant difference of expression. Gain- and loss-of-function analyses revealed an inverse correlation between cisplatin resistance and HIST1H3D expression, while a positive correlation was observed with HIST3H2A or HIST3H2B expression. In UM-Cis, HIST3H2A- and HIST3H2B-mediated chromatin remodeling upregulates autophagy status, which results in cisplatin resistance. Additionally, knockdown of HIST3H2A or HIST3H2B downregulated autophagy-activating genes via chromatin compaction of their promoter regions. MiTF, one of the key autophagy regulators upregulated in UM-Cis, negatively regulated transcription of HIST1H3D, suggesting an interplay between chromatin remodeling-dependent cisplatin resistance and autophagy. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, protein expression pattern of the selected histone protein genes were matched with the in vitro data. By examining the relationship between autophagy and chromatin remodeling genes, we identified a set of candidate genes with potential use as markers predicting chemoresistance in OSCC biopsy samples.

Stabilization of Organic Cations in Lead Halide Perovskite Solar Cells Using Phosphine Oxides Derivatives.

Preventing ion migration in perovskite photovoltaics is key to achieving stable and efficient devices. The activation energy for ion migration is affected by the chemical environment surrounding the ions. Thus, the migration of organic cations in lead halide perovskites can be mitigated by engineering their local interactions, for example through hydrogen bonding. Ion migration also leads to ionic losses via interfacial reactions. Undesirable reactivities of the organic cations can be eliminated by introducing protecting groups. In this work, we report bis(2-oxo-3-oxazolidinyl) phosphinic chloride (BOP-Cl) as a perovskite ink additive with the following benefits: (1) The phosphoryl and two oxo groups form six-membered intermolecular hydrogen-bonded rings with the formamidinium cation (FA), mitigating ion migrations. (2) The hydrogen bonding reduces the electrophilicity of the ammonium protons by donating electron density, therefore reducing its reactivity with the surface oxygen on the metal oxide. Furthermore, the molecule can react to form a protecting group on the nucleophilic oxygen at the tin oxide transport layer surface through the elimination of chlorine. As a result, we achieve perovskite solar cells with an efficiency of 25.0% and improved MPP stability T93 = 1200 h at 40-45 °C compared to a control device (T86 = 550 h). In addition, we show a negative correlation between the strength of hydrogen bonding of different phosphine oxide derivatives to the organic cations and the degree of metastable behavior (e.g., initial burn-in) of the device.

Comparison of Chemoembolization Outcomes Using 70-150 µm and 100-300 µm Drug-Eluting Beads in Treating Small Hepatocellular Carcinoma: A Korean Multicenter Study.

OBJECTIVE: To evaluate the outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) according to the size of the beads for the treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 212 patients with a single HCC ≤5 cm from five tertiary institutions. One hundred and nine patients were treated with 70-150-µm doxorubicin DEBs (group A), and 103 patients received 100-300-µm doxorubicin DEBs (group B). The initial tumor response (assessed between 3 weeks and 2 months after DEB-TACE), time to local tumor progression (TTLTP), restricted mean duration of complete response (RMDCR), rate of complications, incidence of post-embolization syndrome, and length of hospital stay were compared between the two groups. Logistic regression was used to analyze prognostic factors for initial tumor response. RESULTS: The initial objective response rates were 91.7% (100/109) and 84.5% (87/103) for groups A and B, respectively (P = 0.101). In the subgroup analysis of tumors ≤3 cm, the initial objective response rates were 94.6% (53/56) and 78.0% (39/50) for groups A and B, respectively (P = 0.012). There was no significant difference in the TTLTP (median, 23.7 months for group A vs. 19.0 months for group B; P = 0.278 [log-rank], 0.190 [multivariable Cox regression]) or RMDCR at 24 months (11.4 months vs. 8.5 months, respectively; P = 0.088). In the subgroup analysis of tumors >3-cm, the RMDCR at 24 months was significantly longer in group A than in group B (11.8 months vs. 5.7 months, P = 0.024). The incidence of mild bile duct dilatation after DEB-TACE was significantly higher in group B than in group A (5.5% [6/109] vs. 18.4% [19/103], P = 0.003). CONCLUSION: DEB-TACE using 70-150-µm microspheres demonstrated a higher initial objective response rate in ≤3-cm HCCs and a longer RMDCR at 24 months in 3.1-5-cm HCCs compared to larger DEBs (100-300-µm).

Real-Time Tunable Gas Sensing Platform Based on SnO2 Nanoparticles Activated by Blue Micro-Light-Emitting Diodes.

Micro-light-emitting diodes (µLEDs) have gained significant interest as an activation source for gas sensors owing to their advantages, including room temperature operation and low power consumption. However, despite these benefits, challenges still exist such as a limited range of detectable gases and slow response. In this study, we present a blue µLED-integrated light-activated gas sensor array based on SnO2 nanoparticles (NPs) that exhibit excellent sensitivity, tunable selectivity, and rapid detection with micro-watt level power consumption. The optimal power for µLED is observed at the highest gas response, supported by finite-difference time-domain simulation. Additionally, we first report the visible light-activated selective detection of reducing gases using noble metal-decorated SnO2 NPs. The noble metals induce catalytic interaction with reducing gases, clearly distinguishing NH3, H2, and C2H5OH. Real-time gas monitoring based on a fully hardware-implemented light-activated sensing array was demonstrated, opening up new avenues for advancements in light-activated electronic nose technologies.

Assessing Glaucoma Severity and Progression in Individuals with Asymmetric Axial Length: An Intrapatient Comparative Study.

PURPOSE: To investigate whether a difference exists in intereye glaucoma severity and progression in patients with asymmetric axial length. DESIGN: Long-term observational study. PARTICIPANTS: Patients older than 20 years with a diagnosis of glaucoma at Seoul National University Hospital, Seoul, Korea, between 2010 and 2020. METHODS: Patients with a diagnosis of glaucoma in both eyes with an axial length difference of more than 1.0 mm were included. Each individual's eyes were classified into longer eye and shorter eye, and the baseline and follow-up clinical data were analyzed using the paired T-test and McNemar test. MAIN OUTCOME MEASURES: Differences in clinical characteristics in patients with asymmetric axial length. RESULTS: A total of 190 eyes of 95 patients with glaucoma with asymmetric axial length were included in the study. The patients' mean age was 51.2 ± 12.3 years, and the mean follow-up period was 10.1 ± 3.9 years. No difference was found in baseline intraocular pressure (IOP) or central corneal thickness between longer eyes and shorter eyes. Among the baseline disc parameters, ovality index, ß-zone and γ-zone parapapillary atrophy (PPA) area were larger (P < 0.001) in the longer eyes. In the baseline OCT data, the retinal nerve fiber layer (RNFL) thickness (P = 0.009) and ganglion cell-inner plexiform layer (GCIPL) thickness (P < 0.001) were thinner in the longer eyes. According to a baseline visual field (VF) test, the mean deviation and VF index (VFI) values were significantly lower (P < 0.001, P = 0.034) in the longer eyes. Based on an analysis of glaucoma progression, the rate of change of superior GCIPL (longer eyes, -0.65 µm/year; shorter eyes, -0.40 µm/year), mean deviation (longer eyes, -0.40 dB/year; shorter eyes, -0.21 dB/year), and VFI (longer eyes, -0.92%/year; shorter eyes, -0.46%/year) were larger (P = 0.006, P = 0.005, P < 0.001) in the longer eyes. Additionally, the greater the difference in IOP fluctuation, the greater the difference in the rate of change between mean deviation and VFI. CONCLUSIONS: When an axial length difference of more than 1.0 mm was present, glaucoma tended to be more severe and to progress faster in the longer eyes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Sex-Specific Risk Factors and Clinical Dementia Outcomes for White Matter Hyperintensities in a large South Korean Cohort.

Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion: Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Development of Clindamycin-Releasing Polyvinyl Alcohol Hydrogel with Self-Healing Property for the Effective Treatment of Biofilm-Infected Wounds.

Self-healing hydrogels have good mechanical strength, can endure greater external force, and have the ability to heal independently, resulting in a strong bond between the wound and the material. Bacterial biofilm infections are life-threatening. Clindamycin (Cly) can be produced in the form of a self-healing hydrogel preparation. It is noteworthy that the antibacterial self-healing hydrogels show great promise as a wound dressing for bacterial biofilm infection. In this study, we developed a polyvinyl alcohol/borax (PVA/B) self-healing hydrogel wound dressing that releases Cly. Four ratios of PVA, B, and Cly were used to make self-healing hydrogels: F1 (4%:0.8%:1%), F2 (4%:1.2%:1%), F3 (1.6%:1%), and F4 (4%:1.6%:0). The results showed that F4 had the best physicochemical properties, including a self-healing duration of 11.81 ± 0.34 min, swelling ratio of 85.99 ± 0.12%, pH value of 7.63 ± 0.32, and drug loading of 98.34 ± 11.47%. The B-O-C cross-linking between PVA and borax caused self-healing, according to FTIR spectra. The F4 formula had a more equal pore structure in the SEM image. The PVA/B-Cly self-healing hydrogel remained stable at 6 ± 2 °C for 28 days throughout the stability test. The Korsmeyer-Peppas model released Cly by Fickian diffusion. In biofilm-infected mouse wounds, PVA/B-Cly enhanced wound healing and re-epithelialization. Our results indicate that the PVA/B-Cly produced in this work has reliable physicochemical properties for biofilm-infected wound therapy.

Long-Term Outcome of Time-Staged Gamma Knife Radiosurgery for Large Arteriovenous Malformations.

BACKGROUND: Treatment for large (> 10 mL) arteriovenous malformations (AVMs) remains highly challenging. This study evaluated long-term effect of time-staged gamma knife radiosurgery (GKS) for large AVMs. METHODS: For patients with large AVMs treated by time-staged GKS over 10 years, time-staged GKS was repeated every three years targeting the entire nidus if total obliteration was not achieved. Obliteration rate and post-GKS complications were assessed based on 10 mL volume interval of AVMs. Prognostic factors for these outcomes were evaluated using Cox regression analysis. RESULTS: Ninety-six patients were analyzed. For AVMs in the 10-20 mL subgroup, a dose ≥ 13.5Gy yielded higher obliteration rate in the first GKS. In the 20-30 mL subgroup, a second GKS significantly boosted obliteration. AVMs > 30 mL did not achieve any obliteration with the first GKS. Among 35 (36.4%) cases lost to follow-up, 7 (7.2%) were lost due to GKS complications. Kaplan-Meier analysis showed that each subgroup needed different time for achieving 50% favorable obliteration outcome rate: 3.5, 6.5, and 8.2 years for 10-20 mL, 20-30 mL, and > 30 mL subgroup, respectively. Total obliteration rate calculated by intention-to-treat method: 73%, 51.7%, 35.7%, respectively, 61.5% overall. Post-GKS hemorrhage and chronic encapsulated expanding hematoma (CEEH) occurred in 13.5% and 8.3% of cases, respectively. Two patients died. Dose and volume were significant prognostic factors for obliteration. Initial AVM volume was a significant prognostic factor of post-GKS hemorrhage and CEEH. CONCLUSION: Time-staged GKS for large AVMs less than 30 mL has highly favorable long-term outcome and a tolerable complication rate.

The Cell-Penetrating Peptide GV1001 Enhances Bone Formation via Pin1-Mediated Augmentation of Runx2 and Osterix Stability.

Peptide-based drug development is a promising direction due to its excellent biological activity, minimal immunogenicity, high in vivo stability, and efficient tissue penetrability. GV1001, an amphiphilic peptide, has proven effective as an anti-cancer vaccine, but its effect on osteoblast differentiation is unknown. To identify proteins interacting with GV1001, biotin-conjugated GV1001 was constructed and confirmed by mass spectrometry. Proteomic analyses were performed to determine GV1001's interaction with osteogenic proteins. GV1001 was highly associated with peptidyl-prolyl isomerase A and co-immunoprecipitation assays revealed that GV1001 bound to peptidyl-prolyl cis-trans isomerase 1 (Pin1). GV1001 significantly increased alkaline phosphatase (ALP) activity, bone nodule formation, and the expression of osteogenic gene markers. GV1001-induced osteogenic activity was enhanced by Pin1 overexpression and abolished by Pin1 knockdown. GV1001 increased the protein stability and transcriptional activity of Runx2 and Osterix. Importantly, GV1001 administration enhanced bone mass density in the OVX mouse model, as verified by µCT analysis. GV1001 demonstrated protective effects against bone loss in OVX mice by upregulating osteogenic differentiation via the Pin1-mediated protein stabilization of Runx2 and Osterix. GV1001 could be a potential candidate with anabolic effects for the prevention and treatment of osteoporosis.

The Role of Robotics in Meeting Institutional Goals: A Unified Strategy to Facilitate Program Excellence.

PURPOSE: The rapid expansion of robotic surgical equipment necessitates a review of the needs and challenges faced by hospitals introducing robots for the first time to compete with experienced institutions. The aim of this study was to analyze the impact of robotic surgery on our hospital compared to open and laparoscopic surgery, examine internal transformations, and assess regional, domestic, and international implications. METHODS: A retrospective review was conducted of electronic medical records (EMRs) from 2019 to 2022 at Inha University Hospital, including patients who underwent common robotic procedures and equivalent open and laparoscopic operations. The study investigated clinical and operational performance changes in the hospital after the introduction of robotic technology. It also evaluated the operational effectiveness of robot implementation in local, national, and international contexts. To facilitate comparison with other hospitals, the data were transmitted to Intuitive Surgical, Inc. for analysis. The study was conducted in compliance with domestic personal information regulations and received approval from our Institutional Review Board. RESULTS: We analyzed EMR data from 3,147 patients who underwent surgical treatment. Over a period of 3.5 years, the adoption of robotic technology in a hospital setting significantly enhanced the technical skills of all professors involved. The introduction of robotic systems led to increased patient utilization of conventional surgical techniques, as well as a rise in the number of patients choosing robotic surgery. This collective trend contributed to an overall increase in patient numbers. This favorable evaluation of the operational effectiveness of our hospital's robot implementation in the context of local, national, and global factors is expected to positively influence policy changes. CONCLUSION: Stakeholders should embrace data science and evidence-based techniques to generate valuable insights from objective data, assess the health of robot-assisted surgery programs, and identify opportunities for improvement and excellence.

Interventional Radiology for Bleeding Ectopic Varices: Individualized Approach Based on Vascular Anatomy.

Ectopic varices are rare but potentially life-threatening conditions usually resulting from a combination of global portal hypertension and local occlusive components. As imaging, innovative devices, and interventional radiologic techniques evolve and are more widely adopted, interventional radiology is becoming essential in the management of ectopic varices. The interventional radiologist starts by diagnosing the underlying causes of portal hypertension and evaluating the afferent and efferent veins of ectopic varices with CT. If decompensated portal hypertension is causing ectopic varices, placement of a transjugular intrahepatic portosystemic shunt is considered the first-line treatment, although this treatment alone may not be effective in managing ectopic variceal bleeding because it may not sufficiently resolve focal mesenteric venous obstruction causing ectopic varices. Therefore, additional variceal embolization should be considered after placement of a transjugular intrahepatic portosystemic shunt. Retrograde transvenous obliteration can serve as a definitive treatment when the efferent vein connected to the systemic vein is accessible. Antegrade transvenous obliteration is a vital component of interventional radiologic management of ectopic varices because ectopic varices often exhibit complex anatomy and commonly lack catheterizable portosystemic shunts. Superficial veins of the portal venous system such as recanalized umbilical veins may provide safe access for antegrade transvenous obliteration. Given the absence of consensus and guidelines, a multidisciplinary team approach is essential for the individualized management of ectopic varices. Interventional radiologists must be knowledgeable about the anatomy and hemodynamic characteristics of ectopic varices based on CT images and be prepared to consider appropriate options for each specific situation. ©RSNA, 2024 Supplemental material is available for this article.