High mobility group box 1 in the central nervous system: regeneration hidden beneath inflammation.

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields, including neurology and neuroscience. High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern, which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke, Alzheimer's disease, frontotemporal dementia, Parkinson's disease, multiple sclerosis, epilepsy, and traumatic brain injury. Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern, such as glycyrrhizin, ethyl pyruvate, and neutralizing anti-high-mobility group box 1 antibodies, are commonly used to target high-mobility group box 1 activity in central nervous system disorders. Although it is commonly known for its detrimental inflammatory effect, high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders. In this narrative review, we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern, its downstream receptors, and intracellular signaling pathways, how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system, and clues on how to differentiate the pro-regenerative from the pro-inflammatory role. Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

Comparative proteomic analysis of donor human milk treated by high-pressure processing or Holder pasteurization on undigested proteins across dynamic simulated preterm infant digestion.

High-pressure processing (HPP) of donor human milk (DM) minimally impacts the concentration and bioactivity of some important bioactive proteins including lactoferrin, and bile salt-stimulated lipase (BSSL) compared to Holder pasteurization (HoP), yet the impact of HPP and subsequent digestion on the full array of proteins detectable by proteomics remains unclear. We investigated how HPP impacts undigested proteins in DM post-processing and across digestion by proteomic analysis. Each pool of milk (n = 3) remained raw, or was treated by HPP (500 MPa, 10 min) or HoP (62.5 °C, 30 min), and underwent dynamic in vitro digestion simulating the preterm infant. In the meal, major proteins were minimally changed post-processing. HPP-treated milk proteins better resisted proximal digestion (except for immunoglobulins, jejunum 180 min) and the extent of undigested proteins after gastric digestion of major proteins in HPP-treated milk was more similar to raw (e.g., BSSL, lactoferrin, macrophage-receptor-1, CD14, complement-c3/c4, xanthine dehydrogenase) than HoP.

Experimental Investigation into the Mechanical and Piezoresistive Sensing Properties of Recycled Carbon-Fiber-Reinforced Polymer Composites for Self-Sensing Applications.

This study investigates the mechanical and piezoresistive sensing properties of recycled carbon-fiber-reinforced polymer composites (rCFRPs) for self-sensing applications, which were prepared from recycled carbon fibers (rCFs) with fiber lengths of 6, 12, 18, and 24 mm using a vacuum infusion method. Mechanical properties of the rCFRPs were examined using uniaxial tensile tests, while sensing characteristics were examined by monitoring the in situ electrical resistance under cyclic and low fatigue loads. Longer fibers (24 mm) showed the superior tensile strength (92.6 MPa) and modulus (8.4 GPa), with improvements of 962.1% and 1061.1%, respectively. Shorter fibers (6 mm) demonstrated enhanced sensing capabilities with the highest sensitivity under low fatigue testing (1000 cycles at 10 MPa), showing an average maximum electrical resistance change rate of 0.7315% and a gauge factor of 4.5876. All the composites displayed a stable electrical response under cyclic and low fatigue loadings. These results provide insights into optimizing rCF incorporation, balancing structural integrity with self-sensing capabilities and contributing to the development of sustainable multifunctional materials.

Clopidogrel Versus Aspirin as Chronic Maintenance Antiplatelet Monotherapy in Patients After Percutaneous Coronary Intervention With Chronic Kidney Disease: A Post Hoc Analysis of the HOST-EXAM Trial.

BACKGROUND: Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function. METHODS AND RESULTS: We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m2. The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status (P for interaction=0.889). CONCLUSIONS: During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.

Reproducibility for carotid wall segmentation using T1-weighted DANTE-SPACE sequence on high-resolution 3-T carotid MRI.

BACKGROUND: T1-weighted (T1W) magnetic resonance imaging (MRI) using the delay alternating with nutation for excitation-sampling perfection with application-optimized contrasts using different flip angle evolution (DANTE-SPACE) is the preferred imaging technique for evaluation of the vessel wall. PURPOSE: To evaluate the intra- and inter-rater reproducibility of carotid wall segmentation on T1W DANTE-SPACE in patients with symptomatic (acute stroke or transient ischemic attack) internal carotid artery (ICA) stenosis. MATERIAL AND METHODS: This prospective study included 25 patients with acute (≤3 months) stroke or transient ischemic attack and 50%-99% stenosis of the ICA. All patients underwent 3.0-T high-resolution carotid MRI. Two radiologists independently performed the manual segmentation of the vessel wall and inner lumen of the bilateral carotid artery on DANTE-SPACE. The intraclass correlation coefficient (ICC), Dice similarity coefficient (DSC), and Hausdorff distance (HD) were calculated. RESULTS: The ICCs for intra-rater reproducibility of carotid wall volume, inner lumen volume, and normalized wall index were 0.965, 0.990, and 0.962, respectively. The ICCs for inter-rater reproducibility of carotid wall volume, inner lumen, and normalized wall index were 0.856, 0.981, and 0.904. DSC and HD for intra- and inter-rater reproducibility of carotid wall segmentation were as follows: 0.873 and 0.809 (DSC); and 0.079 and 0.118 (HD), respectively. For evaluation of reproducibility only in the carotid artery with symptomatic stenosis, the ICCs for intra- and inter-rater reproducibility indicated all perfect agreement. CONCLUSION: T1W DANTE-SPACE is a reproducible sequence for evaluation of the carotid wall using carotid MRI in patients with symptomatic ICA stenosis.

Tribological properties of real foods using extended Stribeck curves and their relationship with nutritional and rheological parameters.

The tribological properties of 19 commercial food products, grouped into six categories (yogurt, dressings, spreads, porridges, emulsified sauces, and syrups) were investigated in relation to their rheological (dynamic oscillatory shear test) and nutritional properties (fat, carbohydrate, and protein). A tribological system (a glass ball and three polydimethylsiloxane pins) generated the extended Stribeck curve, monitoring friction factors (f) over an extended range of sliding speed (v) (10-8 to 100 m/s). Tribological parameters (f, v) at four inflection points dividing the frictional regimes (X1, breakaway point between the static and kinetic regimes; X1-X2, boundary; X2-X3, mixed; X3-X4, hydrodynamic regimes) and the slope between X3 and X4 (s) were subjected to principal component analysis and hierarchical clustering on principal components, using rheological and nutritional parameters as quantitative supplementary variables. Tribological patterns were predominantly influenced by viscosity, viscoelasticity, yield stress, fat content, and the presence of particles (e.g., sugar, proteins, and fibers) and pasting materials (e.g., starches and modified starches). The 19 tribological patterns were classified into 3 clusters: low f and s for fat- and/or viscoelastic-dominant foods (Cluster 1), low f and high s for food emulsions and/or those with low extent of shear-thinning (Cluster 2), and high f at the boundary regime either for the most viscous foods or for those in the presence of particulates (Cluster 3). These results suggest that the compositional and rheological properties have a more profound impact on the classification of complex tribological patterns than the categories of food products.

Contralateral Hearing Loss in Temporal Bone Fractures: A Potential Association with Combined Intracranial Injury.

Temporal bone (TB) fractures are frequently accompanied by intracranial injury. This study aimed to analyze combined intracranial injuries in relation to functional changes in the inner ear, including those of the contralateral ear, in patients with TB fractures. Ninety-four patients (mean age: 35.6 ± 18.7 years, M : F=67 : 27) diagnosed with unilateral TB fracture were included. Bone conduction (BC) threshold, word recognition score (WRS), and changes in vestibular function were compared based on intracranial injuries, focusing on the contralateral side. Various types of intracranial injuries were observed (67.9%). Among these, a significant association between traumatic brain injury (TBI) and otic capsule-violating fractures was noted. The BC threshold on the fractured side significantly deteriorated in patients with TBI. Additionally, a significantly worse BC threshold was confirmed on the contralateral side in patients with TBI, intracranial hemorrhage (ICH), and contrecoup injury. The follow-up BC threshold did not improve or differ, regardless of high-dose steroid administration. The initial WRS and canal paresis in the bithermal caloric test were not significantly different in the presence of each intracranial injury. Concurrent fluctuations in the pressure of the cerebrospinal fluid space and perilymphatic space were speculated to be the potential underlying mechanisms. A significantly worse BC threshold was confirmed on the contralateral side of patients with TBI, contrecoup injury, ICH, and on fracture sides of patients with TBI.

Deep learning improves quality of intracranial vessel wall MRI for better characterization of potentially culprit plaques.

Intracranial vessel wall imaging (VWI), which requires both high spatial resolution and high signal-to-noise ratio (SNR), is an ideal candidate for deep learning (DL)-based image quality improvement. Conventional VWI (Conv-VWI, voxel size 0.51 × 0.51 × 0.45 mm3) and denoised super-resolution DL-VWI (0.28 × 0.28 × 0.45 mm3) of 117 patients were analyzed in this retrospective study. Quality of the images were compared qualitatively and quantitatively. Diagnostic performance for identifying potentially culprit atherosclerotic plaques, using lesion enhancement and presence of intraplaque hemorrhage (IPH), was evaluated. DL-VWI significantly outperformed Conv-VWI in all image quality ratings (all P < .001). DL-VWI demonstrated higher SNR and contrast-to-noise ratio (CNR) than Conv-VWI, both in normal walls (basilar artery; SNR 4.83 ± 1.23 vs. 3.02 ± 0.59, P < .001) and lesions (contrast-enhanced images; SNR 22.12 ± 11.68 vs. 8.33 ± 3.26, P < .001). In the assessment of 86 lesions, DL-VWI showed higher confidence of detection (4.56 ± 0.55 vs. 2.62 ± 0.77, P < .001), more concordant IPH characterization (Cohen's Kappa 0.85 vs. 0.59) and greater enhancement. For culprit plaque identification, IPH exhibited higher sensitivity in DL-VWI compared to Conv-VWI (70.6% vs. 23.5%) and excellent specificity (94.3% vs. 94.3%). Deep learning application of intracranial vessel wall images successfully improved the quality and resolution of the images. This aided in detecting vessel wall lesions and intraplaque hemorrhage, and in identifying potentially culprit atherosclerotic plaques.

Risk factors of in-stent restenosis after carotid angioplasty and stenting: long-term follow-up study.

Background: After carotid artery angioplasty with stenting (CAS), it is unclear which risk factors are related to long-term outcomes, including in-stent restenosis (ISR). This study aimed to assess the factors associated with restenosis after CAS with a median follow-up of 35.7 months. Materials and methods: Patients who underwent CAS from January 2013 to December 2018 were included if they had symptomatic or asymptomatic carotid artery stenosis. The carotid Doppler ultrasonography (CDU) was followed up after the procedure. We defined at least 50% restenosis using the criteria that the internal carotid artery (ICA) peak systolic velocity (PSV) was greater than 224 cm/s or the ICA to common carotid artery PSV ratio was higher than 3.4. The risk factors for ISR were also assessed. Results: Of the 189 patients, 122 had symptomatic carotid artery stenosis, and 67 had asymptomatic carotid artery stenosis. Patients were evaluated by CDU for a median of 35.7 months (interquartile range 19.5 to 70.0). Kaplan-Meier analysis showed that the longest time to ISR was 39 months, and ISR-free was better in the asymptomatic CAS group. In all groups, ISR was independently associated with current smoker [adjusted odds ratio (aOR), 3.425; 95% confidence interval (CI), 1.086 to 10.801] and elevated ICA PSV at baseline (aOR, 1.004; 95% CI, 1.001 to 1.007). Conclusion: Independent risk factors for ISR in the CAS group included current smoking and elevated ICA PSV at baseline. In the symptomatic CAS group, alcohol was independently associated with the ISR. ISR did not occur after 39 months from the CAS procedure in our study patients. Future studies with extended follow-up are necessary to fully understand the long-term outcomes of CAS.

Optimization of the QuEChERS-UPLC-APCI-MS/MS method for the analysis of vitamins D and K nanoencapsulated in yogurt.

A novel approach was developed to simultaneously determine the contents of vitamins D2, D3, K1, and K2 in yogurt fortified with nanoencapsulated vitamins D and K. This method combines QuEChERS extraction with UPLC-APCI-MS/MS analysis. Optimization of the QuEChERS process included fine-tuning the addition of salts using response surface methodology based on the Box-Behnken design. Under the optimized conditions, the developed method exhibited an excellent linearity (R2 > 0.999) across concentrations ranging from 0.5 to 500 µg/L. The limits of detection and quantification (LOD and LOQ) were found to be 0.01-0.04 µg/L and 0.04-0.11 µg/L, respectively, with precision, accuracy, and recovery rates exceeding 94.88 %, and accompanied by acceptable relative standard deviations. Comparative analysis with traditional methodologies revealed the significant advantages of the proposed approach. Previous techniques such as liquid-liquid extraction combined with saponification are time-consuming and require high sample quantities. In addition, dispersive liquid-liquid microextraction requires a long analysis time and exhibits a poor sensitivity, particularly in terms of its LOD and LOQ values. In contrast, our method offers a straightforward, efficient, and reliable sample preparation technique suitable for detecting vitamins D2, D3, K1, and K2 in a yogurt matrix. This study not only demonstrates the feasibility of applying the QuEChERS method for stable vitamin quantification in yogurt, but it also represents an innovative contribution to enhancing the detection sensitivity and efficiency in food analysis. By emphasizing these methodological advancements and comparative benefits, this research underscores the significance of adopting advanced analytical approaches in food science.

Association Between the Timing of Atrial Fibrillation Detection and Functional Outcome Following Mechanical Thrombectomy.

BACKGROUND: Atrial fibrillation detected after stroke (AFDAS) refers to the identification of newly diagnosed atrial fibrillation (AF) following an ischemic stroke in patients without known AF (KAF). The objective of this study was to compare the functional outcomes of patients diagnosed with AFDAS and those with KAF who underwent mechanical thrombectomy. METHODS AND RESULTS: We conducted a retrospective analysis of patients who underwent mechanical thrombectomy and with either new AF diagnosed during hospitalization or KAF. We compared the baseline characteristics, clinical, and procedure-related variables between those with AFDAS and KAF. The primary outcome was the achievement of functional independence, defined as a modified Rankin Scale score of 0 to 2, at 3 months after stroke. Of the 252 patients, 101 (40.1%) were classified into the AFDAS group. The KAF group exhibited a higher rate of stroke history compared with the AFDAS group (32.5% versus 13.9%; P=0.001). Tandem occlusion was more common in the KAF group (13.2% versus 5.9%), while M2 occlusion was more common in the AFDAS group (11.3% versus 20.8%). The proportion of patients who achieved functional independence was higher in the AFDAS group (37.7% versus 52.5%; P=0.029). Multivariable analysis showed that AFDAS was associated with a favorable functional outcome (odds ratio, 2.67 [95% CI, 1.39-5.14]; P=0.003). CONCLUSIONS: AFDAS demonstrated a positive association with functional independence in patients with stroke who underwent mechanical thrombectomy and were finally diagnosed to have AF during hospitalization. The observed disparities in occlusion site, intractable thrombus, and history of previous stroke may have contributed to these findings.

Predicting septic shock in obstructive pyelonephritis associated with ureteral stones: A retrospective study.

To identify the best combination of potential predictors of septic shock in patients with obstructive acute pyelonephritis associated with ureteral stones (OAPN-US) according to Sepsis-3 criteria. Patients who underwent percutaneous nephrostomy (PCN) with OAPN-US were retrospectively evaluated. Recursive feature elimination (RFE) was applied to patients with and without septic shock to identify factors associated with the prediction of progression to septic shock. We compared combinations of the selected features based on area under the receiver operating curve (AUROC) to determine which combination was most effective. This study included 81 patients who were treated with PCN due to OAPN-US. A comparison was made between 37 patients with septic shock (SS) and 44 patients without septic shock (NSS). SS group had a higher age, poorer Eastern Cooperative Oncology Group status, and significantly higher levels of positivity in urine cultures and blood cultures. There were also differences in laboratory tests between the 2 groups. Procalcitonin (PCT), international normalized ratio (INR), and absolute lymphocyte count (ALC) were selected based on RFE. We compared the predictive power for SS when each marker was used alone, when 2 markers were combined, and when all 3 markers were combined. Among these combinations, using all 3 variables together yielded the highest AUROC of 0.942. Of the 3 variables, PCT had the highest Gini importance score, indicating that it was the most influential factor. Clinical characteristics were different between the SS and the NSS groups. In patients with OAPN-US, the combination of PCT, ALC, and INR was an excellent predictor of septic shock.

Long-term impacts of COVID-19 in patients with prior heart failure in Korea: A nationwide cohort study using the common data model.

Limited data are available on the long-term prognosis and monitoring period after coronavirus disease 2019 (COVID-19) infection in the population with prior heart failure (HF). We aimed to exam the association of COVID-19 with clinical prognosis in populations with prior HF and evaluate prognosis within 30 days and 30 days to 1 year after infection. Based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea from January 2018 to April 2022, 9,822,577 patients were selected and converted to the Observational Medical Outcomes Partnership-common data model by the Big Data Department of Health Insurance Review and Assessment Service of Korea. In the dataset, 1,565,274 patients exhibited diagnosis of HF based on the International Statistical Classification of Diseases and Related Health Problems 10 codes. They were divided into 2 groups according to COVID-19 infection, and propensity-score-matching analysis was performed. The clinical outcome was all-cause mortality. Among the 1,565,274 patients with an HF diagnosis, 1,152,975 patients were classified into the HF with the COVID-19 group and 412,299 patients in the HF without COVID-19 group. We created 200,780 matched pairs by propensity-score-matching analysis. Within 30 days of COVID-19, the HF with COVID-19 group had a higher risk of all-cause death compared with the HF without COVID-19 group (hazard ratio [HR]: 2.19, 95% confidence interval [CI]: 2.04-2.36, P < .01). Thirty days to 1 year after COVID-19 infection, the HF with COVID-19 group exhibited a higher risk of all-cause death (HR: 2.04, 95% CI: 1.83-2.27, P < .01). In populations with prior HF, COVID-19 is associated with a higher risk of all-cause mortality within 30 days and this risk remains augmented up to 1 year after the acute phase of COVID-19. Our findings suggest that greater attention may be crucial in populations with prior HF for a prolonged period after COVID-19 infection.

Effect of Nurse's detection of neurological deterioration on the prognosis of patients with acute cerebral infarction.

Introduction: There is little evidence about the factors related to the detection of neurological deterioration by nurses. We examined the related factors and therapeutic outcomes of nurses' detections of patient's neurological deterioration. Methods: This was a descriptive retrospective study. We included 549 adult stroke patients who were admitted to the acute stroke unit of a tertiary hospital between May 2018 and December 2019 and had changes in neurological symptoms that were detected by stroke nurses. We measured the following outcomes: stroke lesion progression, early neurological deterioration (increase in the total national institutes of health stroke scale score of 2 points or more, increase in the limb weakness score of 1 point or more, or decrease in the alertness score of 1 point or more), and additional clinical management (increasing intravenous fluids, diagnostic imaging, or neuro-intervention). Data was analyzed by logistic regression. Results: A total of 651 new or aggravating symptoms were detected by nurses. The most detected symptom was motor aggravations (49.2 %). Symptoms were commonly detected during the day shift (51.0 %) and by scheduled neurochecks (71.3 %). Of 132 patients who underwent diagnostic imaging by nurses' detection, 63.6 % cases had stroke lesion progression. Nursing experience over 4 years was positively associated with finding stroke lesion progression (OR: 2.49, 95 % CI = 1.09-5.67). Early neurological deterioration was found in 70.7 %, and it was significantly higher during scheduled neurochecks (OR:2.65, 95 % CI = 1.04-6.72) and in the group of large artery atherosclerosis (OR: 2.19, 95 % CI = 1.06-4.49) Additional clinical management was provided to 49.9 % of detection, and scheduled neurocheks (OR: 4.76, 95 % CI = 2.18-10.39) and changes of alertness (OR: 2.89, 96 % CI = 1.51-5.26) were the significant factors. Conclusion: Stroke nurses were able to detect a large number of stroke lesion progression and early neurological deterioration as well as to provide additional clinical management. Systematic guidelines for qualification of stroke nurses may be beneficial.

Analysis of the spatial and morphological characteristics of oligodendrocytes from images of in vitro culture.

Oligodendrocytes (OLs) are glial cells responsible for the formation of myelin sheaths in the central nervous system. The characteristic features of the oligodendrocyte lineage, ranging from proliferative and migratory oligodendrocyte progenitor cells (OPC) to myelinating mature OLs, can be observed in vitro cultures of OL lineage cells. Here, we introduce a method for analyzing the spatial distribution of OPCs, which reflects their capacity for proliferation and migration, and the morphological complexity of mature OLs, which reflects their capacity for myelin formation, from immunostaining images of in vitro OL cultures. Through the methods described, we have demonstrated the tendency for OPCs to cluster in an environment with epidermal growth factor (EGF), and the differing morphological complexity of mature OLs according to culture medium and duration of differentiation.•The proliferative and migratory characteristics of OPCs can be evaluated by analyzing their spatial distribution.•The myelin-forming capacity of mature OLs can be measured by analyzing their morphological complexity.•Image-based analyses may be a substitute for more convoluted experiments to assess OL function.

The Survival and Financial Benefit of Investigator-Initiated Trials Conducted by Korean Cancer Study Group.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from 6 available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion: Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Human Milk Protein-Derived Bioactive Peptides from In Vitro-Digested Colostrum Exert Antimicrobial Activities against Common Neonatal Pathogens.

Human milk reduces risk for necrotizing enterocolitis in preterm infants. Necrotizing enterocolitis occurs in the ileocecal region where thousands of milk protein-derived peptides have been released from digestion. Digestion-released peptides may exert bioactivity, such as antimicrobial and immunomodulatory activities, in the gut. In this study, we applied mass spectrometry-based peptidomics to characterize peptides present in colostrum before and after in vitro digestion. Sequence-based computational modeling was applied to predict peptides with antimicrobial activity. We identified more peptides in undigested samples, yet the abundances were much higher in the digested samples. Heatmapping demonstrated highly different peptide profiles between undigested and digested samples. Four peptides (αS1-casein [157-163], αS1-casein [157-165], ß-casein [153-159] and plasminogen [591-597]) were selected, synthesized and tested against common pathogenic bacteria associated with necrotizing enterocolitis. All four exhibited bacteriostatic, though not bactericidal, activities against Klebsiella aerogenes, Citrobacter freundii and Serratia marcescens, but not Escherichia coli.

Digestive Profiles of Human Milk, Recombinant Human and Bovine Lactoferrin: Comparing the Retained Intact Protein and Peptide Release.

Lactoferrin (LF) is a major component of human milk. LF supplementation (currently bovine) supports the immune system and helps maintain iron homeostasis in adults. No recombinant human lactoferrin (rhLF) is available for commercial food use. To determine the extent to which rhLF (Effera™) produced by Komagataella phaffii digests similarly to hmLF, a validated in vitro digestion protocol was carried out. Bovine LF (bLF) was used as an additional control, as it is approved for use in various food categories. This study compared the extent of intact protein retention and the profile of peptides released in hmLF, bLF and rhLF (each with low and high iron saturation) across simulated adult gastric and intestinal digestion using gel electrophoresis, ELISA and LC-MS. Intact LF retention across digestion was similar across LF types, but the highest iron-saturated hmLF had greater retention in the simulated gastric fluid than all other sample types. Peptides identified in digested hmLF samples strongly correlated with digested rhLF samples (0.86 < r < 0.92 in the gastric phase and 0.63 < r < 0.70 in the intestinal phase), whereas digested bLF samples were significantly different. These findings support the potential for rhLF as a food ingredient for human consumption.

Liposomal irinotecan, oxaliplatin, and S-1 as first-line therapy for patients with locally advanced or metastatic pancreatic adenocarcinoma (NASOX): A multicenter phase I/IIa study.

INTRODUCTION: This multicenter phase I/IIa study aimed to determine the recommended phase II dose (RP2D) and evaluate the safety and preliminary efficacy of liposomal irinotecan (nal-IRI), oxaliplatin, and S-1 (NASOX) as first-line treatment for advanced pancreatic adenocarcinoma. METHODS: Patients with locally advanced or metastatic pancreatic adenocarcinoma without prior systemic treatment for advanced disease, aged ≥ 19 years, with measurable disease, and Eastern Cooperative Oncology Group performance status of 0-1 were eligible. The primary endpoints were to determine the dose-limiting toxicity (DLT) in the phase I cohort and overall response rate (ORR) in the phase IIa cohort. The intention-to-treat (ITT) analysis included patients who received the RP2D. RESULTS: In phase I, seven patients were screened, and six were assessed for DLT. None experienced DLT during the first cycle. The RP2D was determined as nal-IRI 50 mg/m2 and oxaliplatin 60 mg/m2 on day 1, S-1 40 mg/m2 twice daily on days 1-7 every 14 days. For the ITT (N = 41; 7, and 34 from phases I and IIa, respectively), the most common grade 3-4 treatment-emergent adverse events were neutropenia (31.7 %), enterocolitis (9.8 %), anorexia (7.3 %), and diarrhea (2.4 %). The ORR was 58.5 % (1 complete, and 23 partial responses). Two underwent conversion surgery; both achieved R0 resection. With median follow-up of 17.5 months, median progression-free survival was 6.5 months (95 % confidence interval [CI], 5.0-8.1) and median overall survival was 11.4 months (95 % CI, 9.8-15.5). CONCLUSION: NASOX exhibited a manageable safety profile and encouraging efficacy outcomes consistent with NALIRIFOX, showing potential to replace infusional 5-fluorouracil with oral S-1 in the triplet regimen.

Dual Volume Image Fusion Technique for Anatomical Evaluation of Cavernous Sinus Dural Arteriovenous Fistula: Usefulness for Transvenous Target Segment Embolization.

OBJECTIVE: In this preliminary study, we investigated the value of fusion techniques by flat detector computed tomography based dual volume rotational angiography (DVRA) for the evaluation of the anatomical relationship of cavernous sinus dural arteriovenous fistula (CSDAVF) and assessed the possibility of transvenous target segment embolization. METHODS: Twenty-six patients with CSDAVF supplied by multiple feeders underwent DVRA for each feeding large vessel separately. We assessed the anatomical relationship of feeders, fistula points, and venous drainage with 3 dual volume image fusion techniques. Transvenous embolization was targeted to the segment of fistulous point for preserving those not involved and reducing coil mass effect. RESULTS: Dual vessel multi-planar reconstruction fusion technique could show which segment of the cavernous sinus supplied by feeding arteries. In the dual vessel volume rendering fusion technique, the association between feeding arteries, fistula points, and draining veins of 2 different vessels could be accurately identified in 3 dimensions. In addition, we could visualize the exact anatomical relationship between the components of CSDAVF and skull anatomy with the single vessel fusion technique. Based on various fusion images, target segment embolization was successfully performed in 8 patients. In this group, we achieved complete or near complete occlusion without complications, including cranial nerve palsy. CONCLUSIONS: Detailed anatomical information including accurate fistula point, specific feeding arteries, and draining veins could be obtained with various dual volume image fusion techniques. In addition, the target segment embolization of CSDAVF could be possible with understanding of the precise CSDAVF architectures.