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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 six 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.

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., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

The generation of an oligodendrocyte primary culture model encompassing the diverse stages of the lineage is essential for the in vitro research of oligodendrocyte physiology and pathophysiology. Here, we provide a protocol for generating oligodendrocytes from the neonatal rodent brain. We describe steps for isolating oligodendrocyte progenitor cells (OPCs) through differential centrifugation, their subsequent expansion, passaging, and differentiation. For complete details on the use and execution of this protocol, please refer to Kim et al. 1 ., Competing Interests: Declaration of interests The authors have applied for a patent in the Republic of Korea for the culture method related to this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Extreme weather phenomena caused by climate change have exacerbated soil erosion and the subsequent dispersion of pollutants. Pseudomonas aeruginosa is known to contribute to the remediation of polluted water and reduce the geochemical mobility of heavy metals in contaminated soil. However, studies on the influence of biopolymers produced by soil microbes and P. aeruginosa on physical soil properties and soil erosion are limited. We aimed to investigate the influence of soil microbes on the mitigation of soil erosion and geochemical dispersion of heavy metals using a naturally occurring microbial substance, P. aeruginosa-based biopolymer (PBB). The PBB comprised carboxyl, hydroxyl, and amine surface functional groups; consequently, the biopolymer effectively sequestered Cd (maximum sorption capacity q m  = 45.7 mg/g), Cu (q m  = 26.7 mg/g), Pb (q m  = 64.9 mg/g), and Zn (q m  = 26.1 mg/g) in the solution. The PBB amendment of the soil improved the physical properties associated with soil erosion, increasing soil aggregation stability and shear strength by 41.6% and 36.8%, respectively. The extraction of heavy metals from soil via synthetic precipitate leaching decreased by 54.2% following the PBB amendment, and a negative correlation was observed between soil aggregate stability and heavy metal extraction, indicating that this microbial substance could immobilize pollutants by adsorbing cationic metal ions and inhibiting water-induced disaggregation. In the soil erosion experiments, soil loss and heavy metal extraction decreased by 70.9% and 43.8%, respectively, following the PBB amendment. These aggregation and sorption effects of the PBB underscore the potential of soil microbes to mitigate soil erosion and immobilize the geochemical dispersion of heavy metals, thereby contributing to the conservation of soil and water quality in areas surrounding contaminated slopes and heavy metal-contaminated areas, such as cut slopes, agricultural fields, mine dumps, and dams., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Myoung-Soo Ko reports financial support was provided by National Research Foundation of Korea. Myoung-Soo Ko reports financial support was provided by Korea Institute of Energy Technology Evaluation and Planning. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to compare the complication rates of non-absorbable suture (NAS) and n-butyl-2-cyanoacrylate (NBCA) skin adhesive for skin closure during totally implantable venous access devices (TIVADs) implantation., Methods: Between March 2020 and February 2021, 586 consecutive patients who underwent TIVAD implantation were retrospectively analyzed. Two groups of patients suture with NAS ( n  = 299) or NBCA ( n  = 287) were followed up for 18 months to compare the occurrence of infection, thrombosis, and non-thrombotic malfunction. A total of 364 cases were extracted using propensity score matching in a 1:1 ratio. Mean TIVADs maintenance days were analyzed using Kaplan-Meier survival analysis., Results: Nineteen cases of complications occurred (0.294/1000 catheter-days) in the NAS group and 17 cases (0.210/1000 catheter-days) in the NBCA group. The difference in the complication rates between the two groups was not statistically significant ( p  = 0.725) after propensity score matching. Mean TIVADs maintenance days were 627.3 days in NAS group and 697.6 days in NBCA group. There was no statistically significant difference in the number of TIVADs maintenance days between the two groups ( p  = 0.081)., Conclusion: In TIVADs implantation, skin closure using NBCA showed no difference in the occurrence of infectious complications compared with conventional non-absorbable skin suture., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: This study evaluates the prognostic significance of tumor size at disease progression (PD) and depth of response (DOR) in cancer patients., Materials and Methods: We performed post hoc analysis using data from six prospective clinical trials conducted by the Korean Cancer Study Group. Patients with tumor size at PD was categorized into 'Mild PD' and 'Significant PD' based on the cutoff values of relative change from baseline using maximally selected rank statistics. The overall survival (OS) and progression-free survival (PFS) were compared between PD and DOR categories., Results: Among the 194 evaluable patients, 130 experienced PD. A 35.48% decrease from baseline in tumor size at PD was chosen for the cutoff between mild and significant PD for OS (mild PD: tumor size from the baseline ≤ -35.48%; significant PD > -35.48%). The mild PD had superior OS compared to the significant PD (25.8 vs. 12.8 months; Hazard ratio [HR] 0.47, 95% CI 0.266-0.843, p=0.009). When using an exploratory cutoff based on whether the tumor size was below vs. exceeded from the baseline (mild PD: tumor size from the baseline ≤ 0%; significant PD > 0%), OS remained significantly longer in the mild PD (17.1 vs. 11.8 months; HR 0.60, 95% CI 0.392-0.932, p=0.021). The greatest DOR was associated with the longest OS and PFS (p<0.001 for both)., Conclusion: Tumor size at PD and DOR were significant prognostic factors for progressive disease. Maintaining a sufficiently reduced tumor size even during PD was associated with better survival outcomes.

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/m 2 and oxaliplatin 60 mg/m 2 on day 1, S-1 40 mg/m 2 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CY received honoraria from Servier, Bayer, AstraZeneca, Merck Sharp & Dohme, Eisai, Celgene, Bristol Myers Squibb, Ipsen, Novartis, Boryung Pharmaceuticals, Mundipharma, and Roche; and received research grants from Servier, Bayer, AstraZeneca, Ono Pharmaceuticals, Ipsen, Boryung Pharmaceuticals, and Lunit Inc. C-kL received honoraria from AstraZeneca, Servier, Dong-A ST, Boryung Pharmaceuticals, Mundipharma, and Roche; consulting fees from Roche, and Daiichi Sankyo; and received research grants or supports from Ono Pharmaceuticals, Celltrion, Boryung Pharmaceuticals, GC Biopharma and Lunit Inc. ZW has received grants or contracts from Arcus and Bristol Myers Squibb, consulting fees from Amgen, Arcus, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Ipsen, Merck Sharp & Dohme, and Seagen, support for attending meetings or travel from Amgen, Bayer, and Merck Sharp & Dohme, and has participated on a data safety monitoring board or advisory board for Mirati and Pfizer. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Oligodendrocytes (OL) are myelin-forming glial cells in the central nervous system. In vitro primary OL culture models offer the benefit of a more readily controlled environment that facilitates the examination of diverse OL stages and their intricate dynamics. Although conventional methods for primary OL culture exist, their performance in terms of simplicity and efficiency can be improved. Here, we introduce a novel method for primary OL culture, namely the E3 (easy, efficient, and effective) method, which greatly improves the simplicity and efficiency of the primary OL culture procedure using neonatal rodent brains. We also provided the optimal media composition for the augmentation of oligodendrocyte progenitor cell (OPC) proliferation and more robust maturation into myelin-forming OLs. Overall, E3 offers an undemanding method for obtaining primary OLs with high yield and quality. Alongside its value as a practical tool, in vitro characteristics of the OL lineage additionally identified during the development of the E3 method have implications for advancing research on OL physiology and pathophysiology., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hanki Kim reports financial support was provided by 10.13039/501100003710Korea Health Industry Development Institute. Jun Young Choi reports financial support was provided by 10.13039/501100003710Korea Health Industry Development Institute. Jun Young Choi reports financial support was provided by 10.13039/501100003725National Research Foundation of Korea. Jun Young Choi has patent pending to Ajou University Industry-Academic cooperation Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Retinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea., Methods: This study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates., Results: We identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18-70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06-2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79-51.19) cases/100,000 person-years., Conclusion: The total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75-79 years for total retinal vascular occlusion and retinal vein occlusion, and 80-85 years for central retinal artery occlusion., (© 2024. The Author(s).)

Distribution of arsenic (As) in the environment can occur through various paths, depending on the interrelationship between soil and surface water, and groundwater. This study aimed to identify the origins and pathways of As among various potential origins in soil and water systems using two-dimensional reactive transport models (2D RTMs) and to evaluate the contribution of each origin to the geochemical distribution of As in the study area, which included a reservoir, two streams, and two abandoned mines. The 2D RTMs were prepared by combining hydraulic and geochemical reactive models. The MODFLOW-2005 package was used to simulate the water flow in the study area. The geochemical reaction and distribution of As were simulated using Geochemist's Workbench. The concentration of As in the reservoir was ∼50 μg/L, while that in the soils collected around the mine X and Y was 15.0-1853.2 mg/kg (median: 126.1 mg/kg) and 3.6-1629.2 mg/kg (median: 60.9 mg/kg), respectively. Hydraulic and geochemical input data were derived from field surveys and laboratory experiments. Based on the geochemical and hydrogeological input data, 2D RTMs determined that 32.0 kg of As accumulated into the reservoir over 18 years through surface water, which is from mines X (2.7 kg) and Y (29.3 kg). Hence, mine Y would be the primary origin of As to the reservoir. Based on 2D RTM, 2.4 kg of As entered the reservoir via groundwater (DO <0.1 mg/L). Also, precipitation of sulfide minerals (e.g., orpiment; As 2 S 3 ) influences As dispersion and contribution under subsurface conditions. These modeling results suggest that 2D RTMs could be a new approach for identifying and assessing the contribution of potential As origins in soil and water system., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Myoung-Soo Ko reports financial support was provided by National Research Foundation of Korea., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Surface-enhanced Raman spectroscopy (SERS) is an effective technique for biosensing, enabling label-free detection of biomolecules with enhanced sensitivity. There is a tremendous probability of signal failure in Raman frequencies because of the scattering of the Raman radiation in liquids, effective SERS improvement is required to reduce this issue when considering liquid specimens. We examined a liquid bacterial sample, investigating the electrostatic interactions of the bacterial samples with gold nanorods (AuNRs) and graphene. We established a voltage-gated 3D graphene functionalized with an AuNR-based device on the silicon substrate for SERS measurements when the applied voltage ranges from 0 to 3 V. Moreover, AuNRs density-susceptible bacterial sample analysis with varied concentrations of bacterial samples has also been described. Using bacterial SERS analysis, the bacterial components amide II (1555-1565 cm -1 ) and amide III (1250-1350 cm -1 ) have been discovered for both bacteria, Gram-positive, Listeria monocytogenes and Gram-negative, Salmonella typhi . Our fabricated device affords an interesting label-free, rapid, and reproducible bacterial sample analysis based on the density of the AuNRs when functionalizing flake-like 3D graphene, which can help facilitate label-free bacteria sensing platforms.

Continuous industrial development has increased the demand of energy. Inevitably, the development of energy sources is steadily progressing using various methods. Rather than establishing a new energy source, a system for storing waste heat generated by industry has now been accepted as a useful strategy. Among such systems, the hydration and dehydration reactions of MgO/Mg(OH) 2  are eco-friendly, have relatively low toxicity and risk, and have a large reserves. Therefore, it is a promising candidate for a heat-storage system. In this study, ultrahigh-porosity particles are used to maximize the heat-storage efficiency of pure MgO. Due to its large surface area, the heat storage rate is 90.3% of the theoretical value and the reaction rate is very high. In addition, as structural collapse, likely to be caused by volume changes between reactions, is blocked as the porous region is filled and emptied, the cycle stability is secured. Ultrahigh-porosity MgO microparticles can be used to build eco-friendly heat-storage systems., (© 2022 Wiley-VCH GmbH.)

Purpose: Trastuzumab-containing chemotherapy is the recommended first-line regimen for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. We evaluated the safety and efficacy of trastuzumab combined with ramucirumab and paclitaxel as second-line treatment for HER2-positive G/GEJ cancer., Patients and Methods: Patients with HER2-positive advanced G/GEJ cancer who progressed after first-line treatment with trastuzumab-containing chemotherapy were enrolled from five centers in the Republic of Korea. Patients were administered a 28-day cycle of trastuzumab (once on days 1, 8, 15, and 22: 2 mg/kg followed by 4 mg/kg loading dose), ramucirumab (once on days 1 and 15: 8 mg/kg), and paclitaxel (once on days 1, 8, and 15: dose level 1, 80 mg/m 2 ; or dose level -1, 70 mg/m 2 ). Phase II was conducted with the recommended phase II dose (RP2D). Primary end points were determination of RP2D during phase Ib and investigator-assessed progression-free survival (PFS) in patients treated with RP2D., Results: Dose-limiting toxicity at dose level 1 was not documented during phase Ib, and a full dose combination was selected as the RP2D. Among 50 patients with a median follow-up duration of 27.5 months (95% CI, 17.4 to 37.6), median PFS and overall survival were 7.1 months (95% CI, 4.8 to 9.4) and 13.6 months (95% CI, 9.4 to 17.7), respectively. Objective response rate was 54% (27 of 50, including one complete response), and disease control rate was 96% (48 of 50). Loss of HER2 expression was observed in 34.8% (8 of 23) patients after first-line treatment, and no definite association between HER2 expression and the outcome was revealed. Safety profiles were consistent with previous reports., Conclusion: Trastuzumab combined with ramucirumab and paclitaxel showed appreciable efficacy with manageable safety profiles in patients with previously treated HER2-positive G/GEJ cancer.

Background: Loss of PTEN function leads to increased PI3Kβ signaling. AZD8186, a selective PI3Kβ/δ inhibitor, has shown anti-tumor activity in PTEN-deficient preclinical models. Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed in advanced gastric cancer with PTEN loss., Methods: In the phase Ib dose-escalation, subjects with advanced solid tumors received oral AZD8186 (60 mg or 120 mg; twice daily (BID); 5 days on/2 days off) plus intravenous paclitaxel (70 mg/m2 or 80 mg/m2; days 1, 8, and 15) every 4 weeks. In the phase II part, MRGC patients with PTEN loss or PTEN/PIK3CB gene abnormality were enrolled and received recommended phase II dose (RP2D) of AZD8186 plus paclitaxel. Primary endpoints were to determine maximum tolerated dose (MTD) and RP2D in phase Ib and 4-month progression-free survival (PFS) rate in phase II., Results: In phase Ib, both MTD and RP2D were determined at paclitaxel 80 mg/m2 and AZD8186 120 mg BID. In phase II, 18 patients were enrolled [PTEN loss (n = 18) and PIK3CB mutation (n = 1)]. The 4-month PFS rate was 18.8% (3 of 16 evaluable patients) and further enrollment stopped due to futility., Conclusion: Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed.ClinicalTrials.gov Identifier: NCT04001569., (© The Author(s) 2023. Published by Oxford University Press.)

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline., Competing Interests: Seong-Ho Kong has received research funding from Stryker Co., Ltd. and Medtronic Inc. as the principal investigator and is the CEO of VITCAL, Co., Ltd. No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Korean Gastric Cancer Association.)

A quasi-one-dimensional van der Waals metallic nanowire Nb 2 PdS 6 is synthesized, and its electrical characteristics are analyzed. The chemical vapor transport method is applied to produce centimeter-scale Nb 2 PdS 6 crystals with needle-like structures and X-ray diffraction (XRD) confirms their high crystallinity. Scanning transmission electron microscopy reveals the crystal orientation and atomic arrangement of the specific region with atomic resolution. The electrical properties are examined by delaminating bulk Nb 2 PdS 6 crystals into a few nanometer-scale wires onto 100 nm-SiO 2 /Si substrates using a mechanical exfoliation process. Ohmic behavior is confirmed at the low-field measurements regardless of their thickness variation, and 4.64 nm-thick Nb 2 PdS 6 shows a breakdown current density (J BD ) of 52 MA cm -2 when the high electrical field is delivered. Moreover, with further exfoliation down to a single atomic chain, the J BD of Nb 2 PdS 6 is predicted to have a value of 527 MA cm -2 . The breakdown of Nb 2 PdS 6 proceeds due to the Joule heating mechanism, and the Nb 2 PdS 6 nanowires are well fitted to the 1D thermal dissipating model., (© 2022 Wiley-VCH GmbH.)

The rapid advancement of electrical and telecommunication facilities has resulted in increasing requirements for the development of electromagnetic interference (EMI) shielding composites. Accordingly, an experimental study was conducted to evaluate the EMI shielding performance of carbon nanomaterial (CNM)-embedded carbon-fiber-reinforced polymer (CFRP) or glass-fiber-reinforced polymer (GFRP) composites. Nine combinations of CNMs and carbon or glass fibers were used to fabricate the composites. The synergistic effects of CNMs on the EMI shielding performance were systematically investigated. The results indicated that plate-type CNMs (i.e., graphene and graphite nanoplatelets) have more prominent effects than fiber-type CNMs (carbon nanofibers). The composites fabricated with CFRP afforded higher EMI shielding than the GFRP-based composites. Among the eighteen samples, 3% CNT-GNP in CFRP composites, which included plate-typed CNM, exhibited the best EMI shielding performances, showing 38.6 dB at 0.7 GHz. This study helps understand the shielding performance of CNM-embedded CFRP and GFRP composites in electrical and telecommunication facilities.

Background: Electronic medical records (EMRs) have the highest value among real-world data (RWD). The aim of the present study was to propose a data collection framework of EMR-based RWD to evaluate the effectiveness and safety of cancer drugs by conducting a nationwide real-world study based on the Korean Cancer Study Group., Methods: We considered all patients who received ramucirumab plus paclitaxel (RAM/PTX) for gastric cancer and trastuzumab emtansine (T-DM1) for breast cancer at relevant institutions in South Korea. Standard operating procedures for systematic data collection were prospectively developed. Investigator reliability was evaluated using the concordance rate between the recommended input value for representative fictional cases and the input value of each investigator. Reliability of collected data was evaluated twice during the study period at three institutions randomly selected using the concordance rate between the previously collected data and data collected by an independent investigator. The reliability results of the investigators and collected data were used for revision of the electronic data capture system and site training., Results: Between the starting date of medical insurance coverage and December 2018, a total of 1063 patients at 56 institutions in the RAM/PTX cohort and 824 patients at 60 institutions in the T-DM1 cohort were included. Mean investigator reliability in the RAM/PTX and T-DM1 cohorts was 73.5% and 71.9%, respectively. Mean reliability of collected data in the RAM/PTX and T-DM1 cohort was 90.0% for both cohorts in the first analysis and 89.0% and 84.0% in the second analysis, respectively. Mean missing values of the RAM/PTX and T-DM1 cohorts at the time of simulation of fictional cases and final data analysis decreased from 20.7% to 0.46% and from 18.5% to 0.76%, respectively., Conclusion: This real-world study provides a framework that ensures relevance and reliability of EMR-based RWD for evaluating the effectiveness and safety of cancer drugs., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2022.)

In this study, Nb 2 Se 9 , a one-dimensional (1D) material with van der Waals (vdWs) bonding, was synthesized by chemical vapor deposition (CVD). A liquid precursor was used to overcome the difficulty of controlling the length and density of Nb 2 Se 9 by CVD due to the high melting point of Nb. Growth proceeded horizontally in a nano-ribbon shape on the substrate in the [100] direction, which had the most stable bonding distance, resulting in a preferred orientation of the (010) plane on the out-of-plane axis. Unlike that grown by conventional mechanical or chemical exfoliation, the nanoscale Nb 2 Se 9 grown by CVD was uniform and did not have contaminants, such as dispersants, on its surface, meaning it could effectively induce reactions such as gas adsorption and desorption. It exhibited high sensitivity to NO 2 gas adsorption at room temperature (27 °C), and its behavior was confirmed in a high-humidity environment. For the first time, this study demonstrated the possibility of synthesizing a vdWs bonding-based 1D material by CVD, which is expected to be widely used in a variety of low-dimensional materials and devices.

Over the past few years, many efforts have been devoted to growing single-crystal graphene due to its great potential in future applications. However, a number of issues remain for single-crystal graphene growth, such as control of nanoscale defects and the substrate-dependent nonuniformity of graphene quality. In this work, we demonstrate a possible route toward single-crystal graphene by combining aligned nucleation of graphene nanograins on Cu/Ni (111) and sequential heat treatment over pregrown graphene grains. By use of a mobile hot-wire CVD system, prealigned grains were stitched into one continuous film with up to ∼97% single-crystal domains, compared to graphene grown on polycrystalline Cu, which was predominantly high-angle tilt boundary (HATB) domains. The single-crystal-like graphene showed remarkably high thermal conductivity and carrier mobility of ∼1349 W/mK at 350 K and ∼33 600 (38 400) cm 2 V -1 s -1 for electrons (holes), respectively, which indicates that the crystallinity is high due to suppression of HATB domains.

Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development., (© 2022 The Authors.)

Background: A subgroup analysis of data from a nationwide study (KCSG-ST19-16) was performed to evaluate the efficacy and safety of second-line ramucirumab plus paclitaxel treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma., Methods: The KCSG-ST19-16 study enrolled a total of 1063 patients from 56 hospitals in South Korea with advanced gastric or GEJ adenocarcinoma, who had received second-line treatment with ramucirumab plus paclitaxel. HER2 status was known for 994 (93.5%) of these patients, who were thus included in the subgroup analysis., Results: In total, 163 of 994 patients (16.4%), had HER2-positive gastric or GEJ adenocarcinoma. The objective response rate to ramucirumab plus paclitaxel treatment was significantly higher in patients with HER2-positive disease compared to those with HER2-negative disease (23.0% [95% confidence interval (CI), 15.9-30.1] vs. 15.1% [95% CI, 12.3-17.9], p = 0.025). The median progression-free survival was longer in patients with HER2-positive versus HER2-negative disease, but the difference was not statistically significant (4.3 months [95% CI, 3.7-5.3] vs 3.7 months [95% CI, 3.4-4.0], p = 0.054). There was no statistically significant difference in median overall survival (OS) between the groups (9.8 months [95% CI, 8.9-12.3] vs 10.1 months [95% CI, 9.2-10.9], p = 0.564)., Conclusions: In patients with HER2-positive gastric or GEJ adenocarcinoma, the objective response rate to second-line treatment with ramucirumab plus paclitaxel was significantly higher compared to patients with HER2-negative disease. However, an increased response to treatment was not associated with an improvement in OS., (© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: GV1001 is a human telomerase peptide vaccine that induces a CD4/CD8 T-cell response against cancer cells, thereby affording an immunological anti-tumor effect. Here, we evaluated the efficacy and safety of GV1001 in combination with chemotherapy in patients with metastatic colorectal cancer who had failed first-line chemotherapy. Methods: This multicenter, non-randomized, single-arm phase II study recruited recurrent or metastatic colorectal cancer patients with measurable disease who had failed first-line chemotherapy. Patients received GV1001 and chemotherapy concomitantly based on a pre-established schedule. Cytotoxic chemotherapy and targeted agents (bevacizumab, cetuximab, or aflibercept) were allowed to be used at the discretion of the investigator. The primary endpoint was the disease control rate; secondary endpoints were the objective response rate, progression-free survival, overall survival, and safety outcomes. The baseline serum eotaxin level (a potential predictive biomarker of GV1001) was analyzed. To determine whether an adequate immune response had been induced, a delayed-type hypersensitivity test and a T-cell proliferation test were performed. Results: From May 13, 2015 to October 13, 2020, 56 patients with recurrent or metastatic colorectal cancer treated in seven hospitals of South Korea were enrolled. The median patient age was 64 years (range, 29-82 years); 67.9% were men. Of all patients, 66.1% had left-side colorectal cancer and the RAS mutation was present in 25%. The disease control rate and the objective response rates were 90.9% (95% confidence interval [CI]: 82.4-99.4%) and 34.1% (95% CI, 20.1-48.1%), respectively. The median progression-free survival was 7.1 months (95% CI, 5.2-9.1 months) and the median overall survival was 12.8 months (95% CI, 9.9-15.8 months). The most common all-grade adverse events were neutropenia (48.2%), nausea (26.8%), neuropathy (25.0%), stomatitis (21.4%), and diarrhea (21.4%). Immune response analysis showed that no patient had positive delayed-type hypersensitivity test results; antigen-specific T-cell proliferation was observed in only 28% of patients. The baseline eotaxin level was not associated with any efficacy outcome. Conclusion: Although no clear GV1001-specific immune response was observed, the addition of GV1001 vaccination to chemotherapy was tolerable and associated with modest efficacy outcomes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

We analyzed fundus images to identify whether convolutional neural networks (CNNs) can discriminate between right and left fundus images. We gathered 98,038 fundus photographs from the Gyeongsang National University Changwon Hospital, South Korea, and augmented these with the Ocular Disease Intelligent Recognition dataset. We created eight combinations of image sets to train CNNs. Class activation mapping was used to identify the discriminative image regions used by the CNNs. CNNs identified right and left fundus images with high accuracy (more than 99.3% in the Gyeongsang National University Changwon Hospital dataset and 91.1% in the Ocular Disease Intelligent Recognition dataset) regardless of whether the images were flipped horizontally. The depth and complexity of the CNN affected the accuracy (DenseNet121: 99.91%, ResNet50: 99.86%, and VGG19: 99.37%). DenseNet121 did not discriminate images composed of only left eyes (55.1%, p = 0.548). Class activation mapping identified the macula as the discriminative region used by the CNNs. Several previous studies used the flipping method to augment data in fundus photographs. However, such photographs are distinct from non-flipped images. This asymmetry could result in undesired bias in machine learning. Therefore, when developing a CNN with fundus photographs, care should be taken when applying data augmentation with flipping., (© 2022. The Author(s).)

We synthesized ternary composition chalcogenide Ta 2 NiSe 7 , a quasi-one-dimensional (Q1D) material with excellent crystallinity. To utilize the excellent electrical conductivity property of Ta 2 NiSe 7 , the breakdown current density ( J BD ) according to thickness change through mechanical exfoliation was measured. It was confirmed that as the thickness decreased, the maximum breakdown voltage ( V BD ) increased, and at 18 nm thickness, 35 MA cm -2 of J BD was measured, which was 35 times higher than that of copper, which is commonly used as an interconnect material. By optimization of the exfoliation process, it is expected that through a theoretical model fitting, the J BD can be increased to about 356 MA cm -2 . It is expected that the low-dimensional materials with ternary compositions proposed through this experiment can be used as candidates for current-carrying materials that are required for the miniaturization of various electronic devices.

Recently, ternary transition metal chalcogenides Ta 2 X 3 Se 8 (X = Pd or Pt) have attracted great interest as a class of emerging one-dimensional (1D) van der Waals (vdW) materials. In particular, Ta 2 Pd 3 Se 8 has been actively studied owing to its excellent charge transport properties as an n-type semiconductor and ultralong ballistic phonon transport properties. Compared to subsequent studies on the Pd-containing material, Ta 2 Pt 3 Se 8 , another member of this class of materials has been considerably less explored despite its promising electrical properties as a p-type semiconductor. Herein, we demonstrate the electrical properties of Ta 2 Pt 3 Se 8 as a promising channel material for nanoelectronic applications. High-quality bulk Ta 2 Pt 3 Se 8 single crystals were successfully synthesized by a one-step vapor transport reaction. Scanning Kelvin probe microscopy measurements were used to investigate the surface potential difference and work function of the Ta 2 Pt 3 Se 8 nanoribbons of various thicknesses. Field-effect transistors fabricated on exfoliated Ta 2 Pt 3 Se 8 nanoribbons exhibited moderate p-type transport properties with a maximum hole mobility of 5 cm 2 V -1 s -1 and an I on / I off ratio of >10 4 . Furthermore, the charge transport mechanism of Ta 2 Pt 3 Se 8 was analyzed by temperature-dependent transport measurements in the temperature range from 90 to 320 K. To include Ta 2 Pt 3 Se 8 in a building block for modern 1D electronics, we demonstrate p-n junction characteristics using the electron beam doping method.

Finding new materials with satisfying all the desired criteria for nanodevices is an extremely difficult work. Here, we introduce a novel Nb 2 Se 9 material as a promising candidate, capable of overcoming some physical limitations, such as a suitable band gap, high carrier mobility, and chemical stability. Unlike graphene, it has a noticeable band gap and no dangling bonds at surfaces that deteriorate transport properties, owing to its molecular chain structure. Using density functional theory (DFT) calculations with deformation potential (DP) theory, we find that the electron mobility of 2D Nb 2 Se 9 across the axis direction reaches up to 2.56 × 10 3 cm 2 V -1 s -1 and is approximately 2.5-6 times higher than the mobility of other 2D materials, such as MoS 2 , black phosphorous, and InSe, at room temperature. Moreover, the mobility of 2D Nb 2 Se 9 is highly anisotropic (μ a /μ c ≈ 6.5). We demonstrate the potential of 2D Nb 2 Se 9 for applications in nanoscale electronic devices and, possibly, mid-infrared photodetectors., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Ramucirumab as monotherapy or in combination with paclitaxel is a second-line treatment option recommended for patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, real-world data from large study cohorts focused on ramucirumab plus paclitaxel in gastric cancer are limited., Methods: The study population comprised all patients with gastric or GEJ cancer who received ramucirumab plus paclitaxel in South Korea between 1 May 2018 and 31 December 2018. We included patients with advanced gastric or GEJ adenocarcinoma and disease progression after first-line platinum and fluoropyrimidine-containing combination chemotherapy., Results: In total, 1063 patients were included in the present study. The objective response rate and disease control rate were 15.1% and 57.7%, respectively. The median progression-free survival was 4.03 months (95% confidence interval, 3.80-4.27) and the median overall survival was 10.03 months (95% confidence interval, 9.33-10.73). Grade 3 or higher treatment-related adverse events with incidence of ⩾5% were neutropenia (35.1%) and anemia (10.5%). Based on multivariable analysis, overall survival was negatively associated with Eastern Cooperative Oncology Group performance status ⩾2, weight loss ⩾10% in the previous 3 months, GEJ of primary tumor, poor or unknown histologic grade, number of metastatic sites ⩾3, presence of peritoneal metastasis, no prior gastrectomy, and time to second-line since first-line treatment <6 months., Conclusion: Our large-scale, nationwide, real-world data analysis of an unselected real-world population adds evidence for the efficacy and safety of second-line ramucirumab plus paclitaxel in patients with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

In this study, high-purity and centimeter-scale bulk Ta 2 Ni 3 Se 8 crystals are obtained by controlling the growth temperature and stoichiometric ratio between tantalum, nickel, and selenium. It is demonstrated that the bulk Ta 2 Ni 3 Se 8 crystals could be effectively exfoliated into a few chain-scale nanowires through simple mechanical exfoliation and liquid-phase exfoliation. Also, the calculation of electronic band structures confirms that Ta 2 Ni 3 Se 8 is a semiconducting material with a small bandgap. A field-effect transistor is successfully fabricated on the mechanically exfoliated Ta 2 Ni 3 Se 8 nanowires. Transport measurements at room temperature reveal that Ta 2 Ni 3 Se 8 nanowires exhibit ambipolar semiconducting behavior with maximum mobilities of 20.3 and 3.52 cm 2 V -1 s -1 for electrons and holes, respectively. The temperature-dependent transport measurement (from 90 to 295 K) confirms the carrier transport mechanism of Ta 2 Ni 3 Se 8 nanowires. Based on these characteristics, the obtained 1D vdW material is expected to be a potential candidate for additional 1D materials as channel materials., (© 2021 Wiley-VCH GmbH.)

Tropomyosin receptor kinase (TRK) fusion is one of the oncogenic driver causes of colon cancer, and tropomyosin 3-neurotrophic receptor tyrosine kinase 1 (TPM3-NTRK1) fusion has been detected in the KM12SM cell line. In the present study, we investigated anticancer mechanisms in the KM12SM cell line using three different form of dovitinib (dovitinib (free base), dovitinib lactate (mono acid), and dovitinib dilactic acid (diacid)) and four TRK inhibitors (LOXO-101, entrectinib, regorafenib, and crizotinib). Exposure of TRK inhibitors at concentrations of 10 nM resulted in the apoptosis of KM12SM cells, whereas regorafenib had no effect. Treatment with all inhibitors except regorafenib also significantly increased the expression levels of the genes nuclear factor-erythroid 2-related factor 2 (NRF2) and glutamyl cysteine ligase catalytic subunit (GCLC) in KM12SM. These drugs significantly reduced expression of the phosphorylated proteins NFκB and COX-2 in the KM12SM cell line, and significantly attenuated KM12SM cell migration, according to a Transwell migration assay. Together, these results suggest that TRK inhibitors block products of carcinogenesis by negatively regulating the NFκB signaling pathway and positively regulating the antioxidant NRF2 signaling pathway., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Abnormal regulation of genes has been closely related to gastric cancer. The characterization of gastric cancer has necessitated the development of new therapeutics as well as the identification of prognostic markers to predict the response to novel drugs. In our study, we used RNA sequencing analyses to show that on gastric cancer tissues to identification of gastric cancer prognostic markers. We specifically chose to study RNF43 because it inhibits gastric cancer-related Wnt/β-catenin signaling by interacting with Wnt receptors. PWWP2B was chosen because it is a gene which is downregulated in gastric cancer. Methods: Utilizing RNA sequencing analysis, we evaluated the mRNA expression profile in gastric cancer patients. Also, we used HAP1 cells which is a human near-haploid cell line derived from the male chronic myelogenous leukemia cell line KBM-7. These cell line has one copy of each gene, ensuring the edited allele will not be masked by additional alleles. We investigated the screening of 1,449 FDA-approved drugs in HAP1, HAP1 RNF43 KO and HAP1 PWWP2B KO cells. RNA sequencing data reveals that RNF43 and PWWP2B expression were down-regulated in recurrence gastric cancer patients. Next, we investigated the anti-cancer effects of selected drugs in RNF43 and PWWP2B down-regulated MKN45 gastric cancer cells and xenograft model. Results: Among these FDA-approved drugs, three drugs (docetaxel trihydrate, pelitinib and uprosertib) showed strong inhibitory effects in RNF43 KO cells and PWWP2B KO cells. In MKN45 xenograft model, tumor volumes were significantly reduced in the docetaxel trihydrate, uprosertib or pelitinib-treated group. Our data demonstrated that RNF43 and PWWP2B are a biomarker that predict recurrence of gastric cancer. Conclusions: Our findings suggest that docetaxel trihydrate, uprosertib and pelitinib could be used as novel therapeutic agents for the prevention and treatment of gastric cancer with a decrease in RNF43 and PWWP2B expression., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Deletions of chromosome 1p36 are the most common telomeric deletions in humans and are associated with an increased risk of orofacial clefting. Deletion/phenotype mapping, combined with data from human and mouse studies, suggests the existence of multiple 1p36 genes associated with orofacial clefting including SKI, PRDM16, PAX7 and GRHL3. The arginine-glutamic acid dipeptide (RE) repeats gene (RERE) is located in the proximal critical region for 1p36 deletion syndrome and encodes a nuclear receptor co-regulator. Pathogenic RERE variants have been shown to cause neurodevelopmental disorder with or without anomalies of the brain, eye or heart (NEDBEH). Cleft lip has previously been described in one individual with NEDBEH. Here we report the first individual with NEDBEH to have a cleft palate. We confirm that RERE is broadly expressed in the palate during mouse embryonic development, and we demonstrate that the majority of RERE-deficient mouse embryos on C57BL/6 background have cleft palate. We go on to show that ablation of Rere in cranial neural crest (CNC) cells, mediated by a Wnt1-Cre, leads to delayed elevation of the palatal shelves and cleft palate and that proliferation of mesenchymal cells in the palatal shelves is significantly reduced in Rereflox/flox; Wnt1-Cre embryos. We conclude that loss of RERE function contributes to the development of orofacial clefts in individuals with proximal 1p36 deletions and NEDBEH and that RERE expression in CNC cells and their derivatives is required for normal palatal development., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: We evaluated the efficacy and safety of gemcitabine in combination with erlotinib and S-1 for the treatment of advanced pancreatic cancer. Methods: Chemotherapy-naïve patients with pathologically-proven locally advanced, recurrent, or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine was administered at 1,000 mg/m 2 intravenously on days 1 and 8, erlotinib was administered at 100 mg/day on days 1-21, and S-1 was administered at 60 mg/m 2 on days 1-14 every 21 days and continued to a maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m 2 was permitted from the second cycle for pre-defined tolerable patients. Results: Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1-8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 32 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The confirmed overall response rate was 12.5% [95% confidence interval (CI), 5.1-28.9%] and the disease control rate was 71.9% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.8-4.6 months) and 6.7 months (95% CI, 3.4-9.9 months), respectively. Conclusion: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Tivantinib has been described as a selective inhibitor of c-Met and is being studied in various types of cancer. In this study, we evaluated the effects of tivantinib on the suppression of gastric cancer (GC) cell migration and apoptosis. We also examined the mechanism of action of tivantinib by oncogenic pathway analysis. We applied an RNA-sequencing approach in 34 GC patients to identify oncogenes that are differentially expressed in GC tissues. To examine the inhibitory effect of tivantinib on GC cells, we conducted apoptosis analysis using an annexin V-APC/PI apoptosis detection kit and trans-well migration assay with human GC cell lines. For oncogenic pathway analysis, Western blot and quantitative real-time PCR analysis were used to detect the expression of proteins and genes before and after tivantinib exposure. In the RNA-sequencing analysis of 34 GC patients, c-Met and VEGFA genes were expressed and positively correlated with each other. Cell migration and apoptosis analysis demonstrated that tivantinib induced the best inhibition effect in SNU620, MKN45 (carries VEGFB mutation), AGS, and MKN28 cells, but not in KATO III (carries VEGFB and VEGFC mutations) cells. Oncogenic pathway analysis showed that tivantinib, in addition to c-Met signaling pathway inhibition, also inhibits VEGF signaling and MYC expression in VEGFA-expressing GC cells. We found that tivantinib has anti-cancer activity not only in GC cells overexpressing c-Met but also in non-c-Met GC cells by inhibition of the VEGF signaling pathway.

Rationale: Macular hole (MH) formation after vitrectomy is rare and it may be due to several mechanisms associated with change of foveolar anatomy by vitrectomy. If a MH develops after vitrectomy, surgical treatments including internal limiting membrane peeling and intravitreal gas injection are usually needed for repair of hole. Spontaneous closure of MH is much rarer., Patient Concerns: A 66-year-old patient had a vitrectomy for rhegmatogenous retinal detachment not involving the macula of the right eye. Eight months after the vitrectomy, the visual acuity decreased and full-thickness defect of macula, epiretinal membrane progression, intraretinal cysts, and flame shape hemorrhage along with superior temporal vascular arcade were observed on fundus examination and optical coherence tomography., Diagnoses: MH and branch retinal vein occlusion (BRVO) accompanying cystoid macular edema (CME) were both present on her right eye. Thus, we planned a surgery for MH repair., Interventions: The status of MH was observed while waiting the surgery schedule. At 2 weeks after detection of the MH, optical coherence tomography showed that intraretinal cysts had decreased in extent and the inner wall of the MH had contracted; 4 weeks later, the MH was closed with a subtle subretinal space., Outcomes: The fovea was well-maintained with a complete closure for 9 months., Lessons: MH formation and spontaneous closure occurred in association with BRVO accompanying CME in a patient who had a vitrectomy. In vitrectomized eyes, physicians should consider the possibility of MH development in association with BRVO, and possible spontaneous closure of the MH in accordance with CME resolution.

Dangling-bond-free two-dimensional (2D) materials can be isolated from the bulk structures of one-dimensional (1D) van der Waals materials to produce edge-defect-free 2D materials. Conventional 2D materials have dangling bonds on their edges, which act as scattering centers that deteriorate the transport properties of carriers. Highly anisotropic 2D sheets, made of 1D van der Waals Nb 2 Se 9 material, have three planar structures depending on the cutting direction of the bulk Nb 2 Se 9 crystal. To investigate the applications of these 2D Nb 2 Se 9 sheets, we calculated the band structures of the three planar sheets and observed that two sheets had nearly direct band gaps, which were only slightly greater (0.01 eV) than the indirect band gaps. These energy differences were smaller than the thermal energy at room temperature. The 2D Nb 2 Se 9 plane with an indirect band gap had the shortest interchain distance for selenium ions among the three planes and exhibited significant interchain interactions on the conduction band. The interchain strain induced an indirect-to-direct band gap transition in the 2D Nb 2 Se 9 sheets. These 2D sheets of Nb 2 Se 9 with direct band gaps also had different band structures because of different interactions between chains, implying that they can have different charge mobilities. We expect these dangling-bond-free 2D Nb 2 Se 9 sheets to be applied in optoelectronic devices because they allow for nearly direct band gaps. They can also be used in mechanical sensors because the band gaps can be controlled by varying the interchain strain., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

We heat-treated an amorphous large-area WO 3 thin film to synthesize high-density, high-quality WO 3 nanorods. The WO 3 nanostructures were effective, especially in reducing gas (hydrogen and helium) atmospheres. By electron microscopy analysis, we confirmed that the thermodynamic energy for forming oxygen vacancies in the [020] direction was low. We could apply self-crosslinked WO 3 nanostructures to practical sensor device fabrication by simply placing the electrodes without complex processes such as transfer and e-beam lithography. It was used for the production of a UV detector, which reacted very fast (∼0.316 s) and was very sensitive to the actual UV-C (261 nm) wavelength. Also, plasmon-based light absorption through the Ag nanoparticle coating resulted in more than 350-fold improvement in the on/off process during UV-C irradiation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A novel semiconductor 1D nanomaterial, Nb 2 Se 9 , was synthesized on a bulk scale via simple vapor transport reaction between niobium and selenium. Needle-like single crystal Nb 2 Se 9 contains numerous single Nb 2 Se 9 chains linked by van der Waals interactions, and we confirmed that a bundle of chains can be easily separated by mechanical cleavage. The exfoliated Nb 2 Se 9 flakes exhibit a quasi-two-dimensional layered structure, and the number of layers can be controlled using the repeated-peeling method. The work function varied depending on the thickness of the Nb 2 Se 9 flakes as determined by scanning Kelvin probe microscopy. Moreover, we first implemented a field effect transistor (FET) based on nanoscale Nb 2 Se 9 flakes and verified that it has p-type semiconductor characteristics. This novel 1D material can form a new family of 2D materials and is expected to play important roles in future nano-electronic devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We studied the optimum dispersion solvent for bulk V 2 Se 9 material, which can be used as a new one-dimensional (1D) material, to separate into 1D chain units. Selected twelve solvents, which have different dielectric constants and surface tensions, were tested to exfoliate bulk V 2 Se 9 into nano-scale chains. The atomic level (∼1 nm, mono-chain) exfoliation of V 2 Se 9 was performed using acetone as the solvent. The dispersion concentration was high in solvents having medium dielectric constants ranging from 20 to 40 with surface tensions ranging from 25 to 35 mJ m -2 . This result is similar to the dispersion results of previous transition metal dichalcogenides (TMDCs) such as MoS 2 , WS 2 , MoSe 2 , MoTe 2 , TaSe 2 , NbSe 2 , and NiTe 2 , indicating that the V 2 Se 9 material and its dispersion to 1D units can be expected to play an important role in opening opportunities for new low-dimensional material studies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Mass production of one-dimensional, V₂Se₉ crystals, was successfully synthesized using the solid-state reaction of vanadium and selenium. Through the mechanical exfoliation method, the bulk V₂Se₉ crystal was easily separated to nanoribbon structure and we have confirmed that as-grown V₂Se₉ crystals consist of innumerable single V₂Se₉ chains linked by van der Waals interaction. The exfoliated V₂Se₉ flakes can be controlled thickness by the repeated-peeling method. In addition, atomic thick nanoribbon structure of V₂Se₉ was also obtained on a 300 nm SiO₂/Si substrate. Scanning Kelvin probe microscopy analysis was used to explore the variation of work function depending on the thickness of V₂Se₉ flakes. We believe that these observations will be of great help in selecting suitable metal contacts for V₂Se₉ and that a V₂Se₉ crystal is expected to have an important role in future nano-electronic devices.

Nb 2 O 5 nanostructures with excellent crystallinities were grown on c -plane sapphire and employed for ultraviolet-(UV)-radiation detection. The triangular radial Nb 2 O 5 grown on the c -sapphire substrate had a 6-fold symmetry with domain matching epitaxy on the substrate. Owing to the radial growth, the nanorods naturally connected when the deposition time increased. This structure can be used as a UV-detector directly by depositing macroscale electrodes without separation of a single nanorod and e-beam lithography process. It was confirmed that electric reactions occur at different UV irradiation wavelengths (254 nm and 365 nm)., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Most of thrombocytopenic pregnant women present mild decrease of platelet counts and have favorable outcome. However, small portion of these cases can show moderate to severe thrombocytopenia and may increase the risk of bleeding during delivery. We investigated the prevalence, causes, and outcomes of pregnancies complicated by moderate to severe thrombocytopenia. We reviewed medical records of pregnant women who were diagnosed with moderate to severe thrombocytopenia (<100 × 10 9 /L) during their pregnancies. A total of 4822 deliveries were performed and 26 patients (0.54%) with moderate to severe thrombocytopenia were identified. The most common cause of moderate to severe thrombocytopenia was immune thrombocytopenia (ITP) (42.3%), followed by gestational thrombocytopenia (GT) (34.6%). Compared to GT, ITP showed lower platelet counts at presentation (52.4 × 10 9 /L vs. 80.5 × 10 9 /L, P  = 0.041). Patients with GT could conduct successful delivery without specific management, and patients with ITP showed favorable delivery outcomes with adequate treatment. In conclusion, the incidence of moderate to severe thrombocytopenia during pregnancy was very low and most common causes were ITP and GT. Patients with moderate to severe thrombocytopenia could have favorable delivery outcomes with adequate treatment.