Transparent Micromesh Patterned OLED Fabricated Using the In-Situ Deposition Process of an Ultrathin Mg:Ag Interconnection Layer.

TOLEDs (transparent organic light-emitting diodes) have emerged as one of the most promising ways to implement next-generation display form factors. Transparent OLEDs can provide new added value to HMDs (head mounted displays), automobiles, smart windows, mobile devices, TVs, etc. through their transparency, which allows objects to be seen from the other side. However, previous approaches using metal thin films have faced limitations in attempting to achieve high transmittance. In this study, TOLEDs were designed using a new cathode structure consisting of an interlayer and an emission pattern layer, and these layers connect the light-emitting part and the nonemitting part by themselves without requiring the use of another interconnection layer. This structure, which was intended to improve transmittance, was implemented by applying an in situ evaporation process that adds only one shadow mask without the need to use any difficult methods. Through this process, the optimal condition was found when the light-emitting part was deposited in a mesh pattern with a length of 120 µm and a width of 80 µm, in which case the transmittance of the TOLED improved by up to 83% while maintaining electro-optical performance. It was also confirmed that this new structure can be applied to flexible devices.

Lysine-homologue substitution: Impact on antimicrobial activity and proteolytic stability of cationic stapled heptapeptides.

Numerous natural antimicrobial peptides (AMPs) exhibit a cationic amphipathic helical conformation, wherein cationic amino acids, such as lysine and arginine, play pivotal roles in antimicrobial activity by aiding initial attraction to negatively charged bacterial membranes. Expanding on our previous work, which introduced a de novo design of amphipathic helices within cationic heptapeptides using an 'all-hydrocarbon peptide stapling' approach, we investigated the impact of lysine-homologue substitution on helix formation, antimicrobial activity, hemolytic activity, and proteolytic stability of these novel AMPs. Our results demonstrate that substituting lysine with ornithine enhances both the antimicrobial activity and proteolytic stability of the stapled heptapeptide AMP series, while maintaining low hemolytic activity. This finding underscores lysine-homologue substitution as a valuable strategy for optimizing the therapeutic potential of diverse cationic AMPs.

Prognostic and predictive impact of sex in locally advanced microsatellite instability high gastric or gastroesophageal junction cancer: An individual patient data pooled analysis of randomized clinical trials.

BACKGROUND: Surgery plus peri-operative/adjuvant chemotherapy is the standard of care for locally advanced GC/GEJC, though with unsatisfactory results. dMMR/MSI-high tumors have better prognosis and scant benefit from chemotherapy as compared to pMMR/MSS ones. The differential outcome of therapies in terms of safety and efficacy according to sex is still debated in GC/GEJC patients. METHODS: We previously performed an individual patient data pooled analysis of MAGIC, CLASSIC, ITACA-S, and ARTIST trials including GC/GEJC patients treated with surgery alone or surgery plus peri-operative/adjuvant chemotherapy to assess the value of MSI status. We performed a secondary analysis investigating the prognostic and predictive role of sex (female versus male) in the pooled analysis dataset in the overall population and patients stratified for MSI status (MSI-high versus MSS/MSI-low). Disease-free (DFS) and overall survival (OS) were calculated. RESULTS: Patients with MSI-high tumors had improved survival as compared to MSS/MSI-low ones irrespective of sex, whereas in those with MSS/MSI-low tumors, females had numerically longer OS and DFS (5-year OS was 63.2% versus 57.6%, HR 0.842; p = 0.058, and 5-year DFS was 55.8% versus 50.8%, HR 0.850; p = 0.0504 in female versus male patients). The numerical difference for the detrimental effect of chemotherapy in MSI-high GC was higher in females than males, while the significant benefit of chemotherapy over surgery alone was confirmed in MSS/MSI-low GC irrespective of sex. CONCLUSIONS: This pooled analysis including four randomized trials highlights a relevant impact of sex in the prognosis and treatment efficacy of MSI-high and MSS/MSI-low non-metastatic GC/GEJC.

Real-world Nationwide Outcomes of Minimally Invasive Surgery for Advanced Gastric Cancer Based on Korean Gastric Cancer Association-Led Survey.

PURPOSE: The study aimed to investigate real-world surgical outcomes of minimally invasive surgery (MIS) for advanced gastric cancer using Korean Gastric Cancer Association (KGCA)-led nationwide data. MATERIALS AND METHODS: A nationwide survey of patients who underwent surgical treatment for gastric cancer in 2019 was conducted by the KGCA. A total of 14,076 patients from 68 institutions underwent surgery, and 4,953 patients diagnosed with pathological stages IB-III gastric cancer were included. Among them, 1,689 patients who underwent MIS (MIS group) and 1,689 who underwent the open approach (open group) were matched using propensity score in a 1:1 ratio. Surgical outcomes were compared, and multivariate analysis was performed to identify the independent factors for overall morbidity. RESULTS: The MIS group had a lower proportion of D2 lymphadenectomy, total omentectomy, and combined resection. However, the number of harvested lymph nodes was higher in the MIS group. Better surgical outcomes, including less blood loss and shorter hospital stay, were observed in the MIS group, and the overall morbidity rate was significantly lower in the MIS group (17.5% vs. 21.9%, P=0.001). The mortality rates did not differ significantly between the 2 groups. In the multivariate analysis, the minimally invasive approach was a significant protective factor against overall morbidity (odds ratio, 0.799; P=0.006). CONCLUSIONS: Based on the Korean nationwide data, MIS for stage IB-III gastric cancer had better short-term outcomes than the open approach, including lower rates of wound complications, intra-abdominal abscesses, and cardiac problems.

Imaging follow-up strategy after endovascular treatment of Intracranial aneurysms: A literature review and guideline recommendations.

OBJECTIVE: Endovascular coil embolization is the primary treatment modality for intracranial aneurysms. However, its long-term durability remains of concern, with a considerable proportion of cases requiring aneurysm reopening and retreatment. Therefore, establishing optimal follow-up imaging protocols is necessary to ensure a durable occlusion. This study aimed to develop guidelines for follow-up imaging strategies after endovascular treatment of intracranial aneurysms. METHODS: A committee comprising members of the Korean Neuroendovascular Society and other relevant societies was formed. A literature review and analyses of the major published guidelines were conducted to gather evidence. A panel of 40 experts convened to achieve a consensus on the recommendations using the modified Delphi method. RESULTS: The panel members reached the following consensus: 1. Schedule the initial follow-up imaging within 3-6 months of treatment. 2. Noninvasive imaging modalities, such as three-dimensional time-of-flight magnetic resonance angiography (MRA) or contrast-enhanced MRA, are alternatives to digital subtraction angiography (DSA) during the first follow-up. 3. Schedule mid-term follow-up imaging at 1, 2, 4, and 6 years after the initial treatment. 4. If noninvasive imaging reveals unstable changes in the treated aneurysms, DSA should be considered. 5. Consider late-term follow-up imaging every 3-5 years for lifelong monitoring of patients with unstable changes or at high risk of recurrence. CONCLUSIONS: The guidelines aim to provide physicians with the information to make informed decisions and provide patients with high-quality care. However, owing to a lack of specific recommendations and scientific data, these guidelines are based on expert consensus and should be considered in conjunction with individual patient characteristics and circumstances.

Streptomyces tagetis sp. nov., a chromomycin producing bacteria isolated from the roots of Tagetes patula.

A novel halotolerant actinobacterium, designated as RG38T, capable of producing black extracellular melanin pigment on SP2 agar, was isolated from the roots of Tagetes patula. Comparative analysis of the 16S rRNA gene sequence revealed the highest similarity to Streptomyces collinus NBRC 12759T (99.3%). Phylogenetic analysis showed that strain RG38T clustered within the genus Streptomyces forming a monophyletic cluster with its close relatives. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and amino-acid identity (AAI) values between strain RG38T and related species within the genus Streptomyces were below the standard threshold for prokaryotic species delineation. The DNA G + C content of the strain RG38T was determined to be 73.3%. The genome size measured 7,150,598 bp comprising 17 contigs and encompassed 6,053 protein coding genes. AntiSMASH analysis of the whole genome revealed 35 putative biosynthetic gene clusters (BGCs) responsible for various secondary metabolites. Among these clusters, two gene clusters exhibited 100% similarity to the chromomycin A3, albaflavenone, and anthracimycin, respectively. These compounds were reported to possess significant anticancer and antibacterial activities. LC-MS-based analysis, coupled with further isolation studies, confirmed the production of chromomycins A2 (1), A3 (2), and their derivatives, along with their antibiotic activities. These findings underscore the potential of this novel strain as a novel resource for the discovery of diverse antimicrobial compounds. This study is the first to report an antimicrobial compound producing Streptomyces species isolated from medicinal plant T. patula. Based on a polyphasic study, the strain RG38T isolated from an unexplored habitat with a high potential for new natural products represents a novel species within the genus Streptomyces. Accordingly, we propose the name Streptomyces tagetis sp. nov. for this novel species, with the type strain is RG38T (=KCTC 49624T = TBRC 15113T).

Assessment of Pharmacokinetic Effects of Herbal Medicines on Escitalopram.

Purpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb-antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant. Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype. Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan- 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang-1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san-1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang-1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups. Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram.

Protective Effects of Red Ginseng Against Tacrine-Induced Hepatotoxicity: An Integrated Approach with Network Pharmacology and Experimental Validation.

Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress. Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins. Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000µg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection. Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.

Antioxidant Efficacy of Hwangryunhaedok-tang through Nrf2 and AMPK Signaling Pathway against Neurological Disorders In Vivo and In Vitro.

Alzheimer's disease (AD) is a representative cause of dementia and is caused by neuronal loss, leading to the accumulation of aberrant neuritic plaques and the formation of neurofibrillary tangles. Oxidative stress is involved in the impaired clearance of amyloid beta (Aß), and Aß-induced oxidative stress causes AD by inducing the formation of neurofibrillary tangles. Hwangryunhaedok-tang (HHT, Kracie K-09®), a traditional herbal medicine prescription, has shown therapeutic effects on various diseases. However, the studies of HHT as a potential treatment for AD are insufficient. Therefore, our study identified the neurological effects and mechanisms of HHT and its key bioactive compounds against Alzheimer's disease in vivo and in vitro. In a 5xFAD mouse model, our study confirmed that HHT attenuated cognitive impairments in the Morris water maze (MWM) test and passive avoidance (PA) test. In addition, the prevention of neuron impairment, reduction in the protein levels of Aß, and inhibition of cell apoptosis were confirmed with brain tissue staining. In HT-22 cells, HHT attenuates tBHP-induced cytotoxicity, ROS generation, and mitochondrial dysfunction. It was verified that HHT exerts a neuroprotective effect by activating signaling pathways interacting with Nrf2, such as MAPK/ERK, PI3K/Akt, and LKB1/AMPK. Among the components, baicalein, a bioavailable compound of HHT, exhibited neuroprotective properties and activated the Akt, AMPK, and Nrf2/HO-1 pathways. Our findings indicate a mechanism for HHT and its major bioavailable compounds to treat and prevent AD and suggest its potential.

Clinical Efficacy of Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: 5-year Results of the SENORITA Trial.

OBJECTIVE: This study aimed to compare laparoscopic standard gastrectomy (LSG) and laparoscopic sentinel node navigation surgery (LSNNS) for EGC in terms of 5-year long-term oncologic outcomes. SUMMARY BACKGROUND DATA: The oncological safety of LSNNS for early gastric cancer (EGC) has not been confirmed. Three-year disease-free survival (DFS), which is the primary endpoint of the phase III multicenter randomized controlled clinical trial (SEntinel Node ORIented Tailored Approach [SENORITA] trial), did not show the non-inferiority of LSNNS relative to LSG. METHODS: The SENORITA trial, a multicenter randomized clinical trial, was designed to show that LSNNS is non-inferior to LSG in terms of 3-year DFS. In the present study, we collected 5-year follow-up data from 527 patients recruited in the SENORITA trial as the full analysis set (FAS). Disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and recurrence patterns were evaluated using the FAS of both LSG (n=269) and LSNNS (n=258). RESULTS: The 5-year DFS was not significantly different between the LSG and LSNNS groups (P=0.0561). During the 5-year follow-up, gastric cancer-related events, such as metachronous cancer, were more frequent in the LSNNS group than in the LSG group. However, ten recurrent cancers in the remnant stomach of both groups were curatively resected by additional gastrectomy and one by additional endoscopic resection. Two of the 198 patients who underwent local resection for stomach preservation based on the LSNNS results developed distant metastasis. However, there was no statistically significant difference in the 5-year OS and DSS (P=0.7403 and P=0.9586, respectively) between the two groups. CONCLUSION: The 5-year DFS, DSS and OS did not differ significantly between the two groups. Considering the benefits of LSNNS on postoperative quality of life, LSNNS could be recommended as an alternative treatment option for EGC.

Highly Transparent Red Organic Light-Emitting Diodes with AZO/Ag/AZO Multilayer Electrode.

Free-form factor optoelectronics is becoming more important for various applications. Specifically, flexible and transparent optoelectronics offers the potential to be adopted in wearable devices in displays, solar cells, or biomedical applications. However, current transparent electrodes are limited in conductivity and flexibility. This study aims to address these challenges and explore potential solutions. For the next-generation transparent conductive electrode, Al-doped zinc oxide (AZO) and silver (AZO/Ag/AZO) deposited by in-line magnetron sputtering without thermal treatment was investigated, and this transparent electrode was used as a transparent organic light-emitting diode (OLED) anode to maximize the transparency characteristics. The experiment and simulation involved adjusting the thickness of Ag and AZO and OLED structure to enhance the transmittance and device performance. The AZO/Ag/AZO with Ag of 12 nm and AZO of 32 nm thickness achieved the results of the highest figure of merit (FOM) (Φ550 = 4.65 mΩ-1) and lowest roughness. The full structure of transparent OLED (TrOLED) with AZO/Ag/AZO anode and Mg:Ag cathode reached 64.84% transmittance at 550 nm, and 300 cd/m2 at about 4 V. The results demonstrate the feasibility of adopting flexible substrates, such as PET, without the need for thermal treatment. This research provides valuable insights into the development of transparent and flexible electronic devices.

An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer.

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools designed to improve clinical outcomes and standardize surgical quality in MITG.

Forsythiaside A Activates AMP-Activated Protein Kinase and Regulates Oxidative Stress via Nrf2 Signaling.

Forsythiaside A (FA) is an active constituent isolated from Forsythia suspensa, a beneficial herb used in traditional medicine known for its antioxidant and anti-inflammatory properties. Although various studies have suggested that FA has the protective effects, its impacts on arachidonic acid (AA) plus iron in vitro models and carbon tetrachloride (CCl4)-induced mouse liver damage in vivo have not been explored. In this study, HepG2 cells were subjected to AA + iron treatment to induce apoptosis and mitochondrial impairment and determine the molecular mechanisms. FA exhibited protective effects by inhibiting cell damage and reactive oxygen species (ROS) production induced by AA + iron, as assessed via immunoblot and flow cytometry analyses. Further molecular investigations revealed that FA resulted in the activation of extracellular-signal-related protein kinase (ERK), which subsequently triggered the activation of AMP-activated protein kinase (AMPK), a critical regulator of cellular oxidative stress. Additionally, FA modulated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which is a significant antioxidant transcription factor regulated by the AMPK pathway. For in vivo studies, mice were orally administered FA and then subjected to induction of CCl4-based hepatotoxicity. The protective effect of FA was confirmed via blood biochemistry and immunohistochemical analyses. In conclusion, our findings demonstrated the protective effects of FA against oxidative stress both in vitro and in vivo, thus indicating that FA is a potential candidate for liver protection. Our study sheds light on the mechanistic pathways involved in the antioxidant effects of FA, highlighting the hepatoprotective potential of naturally occurring compounds in traditional herbs, such as FA.

Association of Bypass Surgery and Mortality in Moyamoya Disease.

Background Patients with moyamoya disease (MMD) have a high risk of stroke or death. We investigated whether extracranial to intracranial bypass surgery can reduce mortality by preventing strokes in patients with MMD. Methods and Results This nationwide retrospective cohort study encompassed patients with MMD registered under the Rare Intractable Diseases program via the Relieved Co-Payment Policy between 2006 and 2019, using the Korean National Health Insurance Service database. Following a 4-year washout period, landmark analyses were employed to assess mortality and stroke occurrence between the bypass surgery group and the nonsurgical control group at specific time points postindex date (1 month and 3, 6, 12, and 36 months). The study included 18 480 patients with MMD (mean age, 40.7 years; male to female ratio, 1:1.86) with a median follow-up of 5.6 years (interquartile range, 2.5-9.3; mean, 6.1 years [SD, 4.0 years]). During 111 775 person-years of follow-up, 265 patients in the bypass surgery group and 1144 patients in the nonsurgical control group died (incidence mortality rate of 618.1 events versus 1660.3 events, respectively, per 105 person-years). The overall adjusted hazard ratio (HR) revealed significantly lower all-cause mortality in the bypass surgery group from the 36-month landmark time point, for any stroke mortality from 3- and 6-month landmark time points, and for hemorrhagic stroke mortality from the 6-month landmark time point. Furthermore, the overall adjusted HRs for hemorrhagic stroke occurrence were beneficially maintained from all 5 landmark time points in the bypass surgery group. Conclusions Bypass surgery in patients with MMD was associated with a lower risk of all-cause and hemorrhagic stroke mortality and hemorrhagic stroke occurrence compared with nonsurgical control.

Analyses of All Small Molecule-Based Pentacene/C60 Organic Photodiodes Using Vacuum Evaporation Method.

The vacuum process using small molecule-based organic materials to make organic photodiodes (OPDIs) will provide many promising features, such as well-defined molecular structure, large scalability, process repeatability, and good compatibility for CMOS integration, compared to the widely used Solution process. We present the performance of planar heterojunction OPDIs based on pentacene as the electron donor and C60 as the electron acceptor. In these devices, MoO3 and BCP interfacial layers were interlaced between the electrodes and the active layer as the electron- and hole-blocking layer, respectively. Typically, BCP played a good role in suppressing the dark current by two orders higher than that without that layer. These devices showed a significant dependence of the performance on the thickness of the pentacene. In particular, with the pentacene thickness of 25 nm, an external quantum efficiency at the 360 nm wavelength according to the peak absorption of C60 was enhanced by 1.5 times due to a cavity effect, compared to that of the non-cavity device. This work shows the importance of a vacuum processing approach based on small molecules for OPDIs, and the possibility of improving the performance via the optimization of the device architecture.

Network-based drug repurposing for HPV-associated cervical cancer.

In women, cervical cancer (CC) is the fourth most common cancer around the world with average cases of 604,000 and 342,000 deaths per year. Approximately 50% of high-grade CC are attributed to human papillomavirus (HPV) types 16 and 18. Chances of CC in HPV-positive patients are 6 times more than HPV-negative patients which demands timely and effective treatment. Repurposing of drugs is considered a viable approach to drug discovery which makes use of existing drugs, thus potentially reducing the time and costs associated with de-novo drug discovery. In this study, we present an integrative drug repurposing framework based on a systems biology-enabled network medicine platform. First, we built an HPV-induced CC protein interaction network named HPV2C following the CC signatures defined by the omics dataset, obtained from GEO database. Second, the drug target interaction (DTI) data obtained from DrugBank, and related databases was used to model the DTI network followed by drug target network proximity analysis of HPV-host associated key targets and DTIs in the human protein interactome. This analysis identified 142 potential anti-HPV repurposable drugs to target HPV induced CC pathways. Third, as per the literature survey 51 of the predicted drugs are already used for CC and 33 of the remaining drugs have anti-viral activity. Gene set enrichment analysis of potential drugs in drug-gene signatures and in HPV-induced CC-specific transcriptomic data in human cell lines additionally validated the predictions. Finally, 13 drug combinations were found using a network based on overlapping exposure. To summarize, the study provides effective network-based technique to quickly identify suitable repurposable drugs and drug combinations that target HPV-associated CC.

Real-World Compliance of Surgical Treatment According to the Korean Gastric Cancer Guideline 2018: Evaluation From the Nationwide Survey Data 2019 in Korea.

PURPOSE: This study evaluated real-world compliance with surgical treatment according to Korea's gastric cancer treatment guidelines. MATERIALS AND METHODS: The 2018 Korean Gastric Cancer Treatment Guidelines were evaluated using the 2019 national survey data for surgically treated gastric cancer based on postoperative pathological results in Korea. In addition, the changes in surgical treatments in 2019 were compared with those in the 2014 national survey data implemented before the publication of the guidelines in 2018. The compliance rate was evaluated according to the algorithm recommended in the 2018 Korean guidelines. RESULTS: The overall compliance rates in 2019 were 83% for gastric resection extent, 87% for lymph node dissection, 100% for surgical approach, and 83% for adjuvant chemotherapy, similar to 2014. Among patients with pathologic stages IB, II, and III disease who underwent total gastrectomy, the incidence of splenectomy was 8.08%, a practice not recommended by the guidelines. The survey findings revealed that 48.66% of the patients who underwent gastrectomy had pathological stage IV disease, which was not recommended by the 2019 guidelines. Compared to that in 2014, the rate of gastrectomy in stage IV patients was 54.53% in 2014. Compliance rates were similar across all regions of Korea, except for gastrectomy in patients with stage IV disease. CONCLUSIONS: Real-world compliance with gastric cancer treatment guidelines was relatively high in Korea.

Long-term Functional and Patient-reported Outcomes Between Intra-corporeal Delta-shaped Gastroduodenostomy and Gastrojejunostomy After Laparoscopic Distal Gastrectomy.

PURPOSE: This study aimed to compare the long-term functional and patient-reported outcomes between intra-corporeal delta-shaped gastroduodenostomy and gastrojejunostomy after laparoscopic distal gastrectomy for gastric cancer. MATERIALS AND METHODS: We retrospectively reviewed clinicopathological data from 616 patients who had undergone laparoscopic distal gastrectomy for stage I gastric cancer between January 2015 and September 2020. Among them, 232 patients who had undergone delta-shaped anastomosis and another 232 who had undergone Billroth II anastomosis were matched using propensity scores. Confounding variables included age, sex, body mass index, physical status classification, tumor location, and T classification. Postoperative complications, nutritional outcomes, endoscopic findings, and quality of life (QoL) were compared between the 2 groups. RESULTS: No significant differences in postoperative complications or nutritional parameters between the two groups were observed. Annual endoscopic findings revealed more residual food and less bile reflux in the delta group (P<0.001) than in the Billroth II group. Changes of QoL were significantly different regarding emotional function, insomnia, diarrhea, reflux symptoms, and dry mouth (P=0.007, P=0.002, P=0.013, P=0.001, and P=0.03, respectively). Among them, the delta group had worse insomnia, reflux symptoms, and dry mouth within three months postoperatively. CONCLUSIONS: Long-term nutritional outcomes and QoL were comparable between the delta and Billroth II groups. However, more residual food and worse short-term QoL regarding insomnia, reflux symptoms, and dry mouth were observed in the delta group. Longer fasting time before endoscopic evaluation and short-term symptom management would have been helpful for the delta group.

Effect of Vitamin B12 Replacement Intervals on Clinical Symptoms and Laboratory Findings in Gastric Cancer Patients after Total Gastrectomy.

The management of patients with vitamin B12 deficiency after total gastrectomy (TG) remains controversial. We aimed to evaluate the effect of vitamin B12 replacement intervals on the clinical characteristics in these patients. The data from patients who received vitamin B12 supplementation after TG between 2007 and 2018 at the National Cancer Center, Korea, were retrospectively evaluated. Vitamin B12 deficiency was defined as a serum vitamin B12 level of <200 pg/mL or urine methylmalonic acid level > 3.8 mg/gCr. The patients were divided into a regular replacement group (patients received an intramuscular injection or oral medication regularly), and a lab-based replacement group (patients received vitamin B12 intermittently after checking the level). The symptoms and biochemical parameters were compared between these groups. The regular and lab-based replacement groups included 190 and 216 patients, respectively. The median vitamin B12 replacement intervals were 1 and 9 months, respectively (p < 0.001). After replacement, the regular replacement group had higher vitamin B12 levels than the lab-based replacement group (p < 0.001). However, the serum hemoglobin level showed no significant changes. After replacement, there was no significant difference in the proportion of the symptomatic patients between the groups. Replacing vitamin B12 with a lab-based protocol may be sufficient for TG patients.

Fibular Fixation in Same-Level Distal Third Tibiofibular Fractures: Is Fibular Fracture Regarded as a Secondary Importance?

Background: Although most studies focused on the alignment or union of the tibia in same-level distal third tibiofibular fractures, the outcome of a concomitant fibular fracture is generally regarded as being of secondary importance in the literature. This study aimed to assess the outcomes of fibular fractures in same-level distal third tibiofibular fractures. Methods: In this retrospective study, we enrolled 111 patients with same-level distal third tibiofibular fractures treated at our institute between January 2016 and August 2020. Tibial fractures were stabilized with intramedullary nailing, and the cases were divided into two groups based on whether they additionally underwent fibular fixation (group 1, 57 cases) or not (group 2, 54 cases). Clinical and radiographic outcomes were used for the evaluation of tibial and fibular alignments, union of the tibia and fibula, number of interlocking screws in the distal tibial fragment, range of motion of the ankle joint, and complications. Results: No statistically significant differences in the tibial union rate or mean tibial alignment were observed between the two groups on either the immediate postoperative or final radiographs. The fibular union rate in group 1 was significantly higher than that in group 2 (fibular nonunion, 0 vs. 15; p < 0.001). Statistically significant differences in fibular displacement were observed on immediate postoperative radiographs between patients with fibular union and those without it. At the final follow-up, the mean range of ankle motion and lower extremity functional scale scores did not differ between the two groups. Conclusions: Regardless of whether fibular fixation was performed, the overall tibial alignment with intramedullary nailing was well restored and the union rate of the tibia was comparable in the two groups. Fibular nonunion is not uncommon in unfixed fibula fractures. Displacement of the fibula as seen on immediate postoperative radiographs was related to fibular nonunion.