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Purpose: The purpose of this study was to investigate the effects of postoperative complications on long-term survival after laparoscopic surgery for resectable colorectal cancer., Methods: We retrospectively included 204 patients who underwent laparoscopic surgery for colorectal cancer from January 2016 to June 2020., Results: Overall, 68 (33.3%) patients had postoperative complications, twelve (17.6%) of which were classified as Clavien-Dindo class 3a or higher. The 5-year overall survival rate of the non-complication and complication groups were 93.0% and 81.7%, respectively (p = 0.048; Kaplan-Meier analysis and log-rank test), and those among patients with stage III disease were 87.0% and 61.3%, respectively (p = 0.045). The 5-year disease-free survival rates were 85.6% and 77.4%, respectively (p = 0.042). Multivariable Cox proportional-hazards analysis revealed that nodal stage (hazard ratio, 8.392; 95% confidence interval, 1.892-37.175; p = 0.005) was an independent prognostic factor for overall survival, and postoperative complications (hazard ratio, 2.996; 95% confidence interval, 1.076-8.340; p = 0.036) were independent prognostic factors for disease-free survival., Conclusion: Postoperative complications were associated with poor oncological outcomes, especially among patients with stage III colorectal cancer, and independent prognostic factors for disease-free survival., (© 2024. The Author(s).)

Background/aims: Few real-world studies explored factors associated with latent tuberculosis infection (LTBI) treatment-related adverse drug reactions (ADRs). This study evaluate ADRs that lead to the discontinuation of LTBI treatment and identify the associated factors, including age groups and drug regimens., Methods: Using the Korean national tuberculosis registry and HHC investigation database linked to the National Health Insurance Service claims database, we examined treatment discontinuation due to ADRs among HHCs on LTBI treatment from January 2015 to December 2018. Multivariable logistic regression analysis was conducted to examine factors associated with ADRs, including demographics, LTBI treatment, comorbidities, and steroid use., Results: Among 11,913 participants initiated LTBI treatment, 633 participants (5.3%) discontinued treatment due to ADRs. The primary contributors to discontinuation were adverse skin reactions (2.0%) and abnormal liver function (1.9%). Risk associated with ADRs and abnormal liver function showed age-related increase, except for the age group 66-75 (adjusted odds ratio [AOR] 3.82, 95% confidence interval [CI] 2.31-6.31) which reported lower OR to that of age group 36-65 (AOR 4.38, 95% CI 3.09-6.21). Three months isoniazid/rifampin and 4 months rifampin exhibited a lower odds of ADRs and abnormal liver function when compared to 6-9 months isoniazid., Conclusion: We discovered the real-world prevalence of LTBI treatment discontinuation due to ADRs among HHCs. Our findings suggest a notably increased odds of ADRs resulting in discontinuation with age of 76 years or above, emphasizing careful attention when prescribing LTBI treatment in this population. Further studies are warranted to validate these results.

Rising health concerns regarding chronic diseases call for exploring natural sources of antioxidants and factors that influence their activity. This study evaluated the diversity of 112 sesame germplasms from Africa and Asia based on ten agronomic traits (seven quantitative and three qualitative), two antioxidant activities (ABTS and DPPH radical scavenging activities), and the content of one metabolite (TPC). TPC, DPPH, and ABTS were in the ranges of 4.98-87.88 µg GAE/mg DE, 3.97-46.23 µg AAE/mg DE, and 3.42-176.01 µg TE/mg DE, respectively. Statistical analyses revealed significant variations in agronomic traits, TPC, and antioxidant activities among the sesame germplasms ( p < 0.05). Furthermore, the individual and interaction effects of seed color and the continent of origin on the levels of the quantitative traits, TPC, ABTS, and DPPH were analyzed, and the correlation among the traits was further evaluated. Diversity in TPC, ABTS, and DPPH was significantly associated with seed color and most of the quantitative agronomic traits ( p < 0.05) but not with continent of origin. Principal component analysis revealed TPC, ABTS, DPPH, and five quantitative traits as the most discriminant traits. In general, six sesame accessions with high TPC and antioxidant activities (IT194356, IT170094, IT29971, IT185998, IT104246, and IT169623) as well as important agronomic traits were identified and, hence, could be used for developing improved sesame varieties.

Objective: The cerebral and spinal venous systems have similar functions but unique anatomical and physiological properties. CSF occupies space in the cranial and spinal vaults, is continuously produced, and has many roles, including maintaining a favorable environment for CNS structures. The influence of the cerebrospinal venous system on CSF dynamics has been theorized since the 1940s. Newer studies suggest venous outflow pattern alterations in response to changes in body position. However, the relationship of postural cerebrospinal venous outflow shifts with and their influence on CSF homeostasis is not well understood., Methods: The authors searched the published literature related to the anatomy and function of vertebral venous plexus (VVP), CSF, and positional cerebral venous flow characteristics. A comprehensive collection of literature was compiled and reviewed, and the relationship between cerebrospinal and venous system changes and alterations in body positions, with an emphasis on the craniocervical system, is discussed., Results: The VVP is a network of valveless veins extending from the sacrum to the cranium that are interconnected with the cranial dural sinuses. The internal VVP occupies space within the extradural spinal canal and functions to return spinal venous blood to the heart, but it has additional properties, including the capability of bidirectional venous flow, an intraspinal dilatory capacity, and a role in cerebral venous outflow. When one rises to the upright position, CSF shifts toward the spinal canal and force vectors change, leading to reduced intracranial CSF pressure; simultaneously, cerebral venous outflow shifts from the jugular vein to the VVP outflow pathway. The venous outflow shift mechanism and its purpose are poorly understood. The authors review the known physiology of the system, identify gaps in knowledge to direct future research, and propose an interpretation of these data, concluding that position-dependent CSF and cerebrospinal venous shifts are part of a complementary positional craniospinal pressure regulation system that must be kept in balance for optimal CNS function., Conclusions: Current knowledge of the cerebrospinal venous anatomy, dynamic flow characteristics in response to gravity, and the venous system's influence on CSF suggests that the VVP plays a role in influencing CSF pressure, and the authors hypothesize that it plays a role in supporting intracranial pressure in the upright body posture. Further research is needed to better characterize the functional relationship of the VVP to CSF dynamics as well as identify potentially related disease states.

This study was conducted to investigate whether lysophosphatidic acid (LPA) could improve the development of porcine somatic cell nuclear transfer (SCNT) embryos. Porcine SCNT-derived embryos were cultured in chemically defined polyvinyl alcohol (PVA)-based porcine zygote medium (PZM)-4 without or with LPA, and the development, cell proliferation potential, apoptosis, and expression levels of pluripotent markers were evaluated. LPA significantly increased the rates of cleavage and blastocyst formation compared to those seen in the LPA un-treatment (control) group. The expression levels of embryonic development-related genes (IGF2R, PCNA and CDH1) were higher ( p < 0.05) in the LPA treatment group than in the control group. LPA significantly increased the numbers of total, inner cell mass and EdU (5-ethynyl-2'-deoxyuridine)-positive cells in porcine SCNT blastocysts compared to those seen in the control group. TUNEL assay showed that LPA significantly reduced the apoptosis rate in porcine SCNT-derived embryos; this was confirmed by decreases ( p < 0.05) in the expression levels of pro-apoptotic genes, BAX and CASP3, and an increase (p < 0.05) in the expression level of the anti-apoptotic gene, BCL2L1. In addition, LPA significantly increased Oct4 expression at the gene and protein levels. Together, our data suggest that LPA improves the quality and development of porcine SCNT-derived embryos by reducing apoptosis and enhancing cell proliferation and pluripotency., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2024 Korean Society of Animal Science and Technology.)

Sesame is an important oilseed crop grown for human consumption in many countries, with a high commercial value due to its high oleic/linoleic acid ratio (O/L ratio). However, its properties may vary among different accessions. In the current study, 282 sesame accessions were evaluated to determine the effects of agronomic traits and genotypes on the O/L ratio. The O/L ratio was positively correlated with the oleic acid (C18:1), stearic acid (C18:0), and myristic acid (C14:0) concentrations, as well as the capsule zone length (CZL), capsule width (CW), and capsule length (CL), and negatively correlated with the linoleic acid (C18:2) and linolenic acid (C18:3) concentrations, the days to maturity (DTM), days to flowering (DTF), and the height of the first capsule-bearing node (HFC) ( p < 0.05). In addition, the O/L ratio was affected by the FAD2 haplotype, as the Hap2 and Hap3 sesame accessions had lower O/L ratios. Therefore, we suggest that the increase and decrease in the contents of C18:1 and C18:2 are associated with the FAD2 haplotype. A total of 25 agronomic traits and fatty acid compositions were compared via statistical analysis, and accessions with a high O/L ratio were selected. The results of this study can be used as a basis for further research on the development of new sesame varieties through enhancing nutritional functionality.

Background: Health care workers (HCWs) face a higher risk of infection and may transmit pathogens to patients during a pandemic. This study aims to evaluate infection-control measures by analyzing the incidence and risk factors of COVID-19 and estimating vaccine effectiveness (VE) at a tertiary hospital in Seoul, Republic of Korea., Methods: This study included 2,516 HCWs from January 1, 2020, to June 30, 2022. Data were analyzed to determine the incidence density and cumulative incidence; the results were compared by the age- and gender-specific standardized incidence ratios (SIR). VE was estimated with multivariate Cox proportional-hazard models as 1-adjusted hazard ratio × 100%., Results: SIR indicated a lower COVID-19 risk in the hospital population than in the general Korean population (SIR, 0.81; 95% confidence interval [CI]: 0.76-0.87). Multivariate Cox analysis indicated that, compared to doctors, nonmedical service supporters and other HCWs (excluding doctors and nurses) were high-risk groups (adjusted hazard ratio [95% CI], 1.72 [1.04-2.83] and 1.76 [1.20-2.58], respectively). Compared to the outpatient unit, the emergency department was a high-risk department (1.70 [1.16-2.50]). The VE of the booster dose was 55.47%, compared to no or incomplete vaccination (95% CI: 22.63-74.37)., Conclusions: Besides encouraging HCWs vaccination, effective infection-control measures should target high-risk groups and departments., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase., Objective: We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age., Methods: We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population., Results: Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors., Conclusions: The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs., (©Yoon Young Choi, Myeongjee Lee, Eun Hwa Kim, Jae Eun Lee, Inkyung Jung, Jae-Ho Cheong. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 08.05.2024.)

A middle-aged patient presented with right-sided chemosis, exophthalmos, and progressive visual loss. Digital subtraction angiography revealed a type D carotid-cavernous fistula (CCF). Transarterial embolization through the internal maxillary artery was unsuccessful, and there was no venous access to the CCF. A robotic-guided direct transtemporal embolization of the CCF with Onyx was performed, resulting in successful fistula obliteration and symptom resolution. This is the first reported case of a robotic-guided direct transcranial CCF embolization. We include a technical video that demonstrates this procedure (Supplemental File 1)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

In this paper, we present a 6-bit phase shifter designed and fabricated using the 150 nm GaN HEMT process. The designed phase shifter operates within the n260 (37~40 GHz) band, as specified in the 5G NR standard, and employs the structure of a switched-filter phase shifter. By serially connecting six single-bit phase shifters, ranging from 180° to 5.625°, the designed phase shifter achieves a phase range of 360°. The fabricated phase shifter exhibits a minimum insertion loss of 5 dB and an RMS phase error of less than 5.36° within the 37 to 40 GHz. This phase shifter is intended for seamless integration with high-power RF circuits.

Objectives: This systematic aimed to understand the global status using the results of survey studies based on the Community Pharmacy Survey on Patient Safety Culture and set the directions of development in terms of the patient safety culture of community pharmacies., Methods: Electronic searches were performed in EMBASE, MEDLINE, PubMed, and CINAHL databases by using the words "patient safety," "culture," and "community pharmacy" with synonyms or associated words in the original English language research articles published between January 1, 2012, and March 2, 2023. This systematic review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: Eleven surveys from 10 countries were selected. Five studies were conducted on pharmacists, whereas 6 studies were carried out on all pharmacy staff members such as pharmacists, technicians, clerks, and pharmacy students on apprenticeship. There was a considerable variation in the positive response rates across the dimensions of all the surveys. The highest positive response score was demonstrated for "teamwork" and "patient counseling," whereas the "staffing, work pressure, and pace" dimension was essential for improving patient safety culture in community pharmacy settings. For overall rating of the pharmacy on patient safety, 84.8% of pharmacy staff members gave good, very good, or excellent as their responses., Conclusions: Despite the differences among studies, findings of this study are expected to be used as valuable evidence to develop patient safety improvement strategies after reflecting each country's health care setting or community pharmacy practice. Furthermore, the results would offer meaningful assistance to achieve the goals of global campaigns such as the World Health Organization Patient Safety Challenge., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Paracavernous dural arteriovenous fistulas (pdAVFs) are extremely rare and can mimic carotid cavernous fistulas (CCFs) in both clinical presentation and imaging characteristics. Access to the venous pouch often presents the greatest challenge in the treatment of pdAVFs. Here we present a novel access technique utilizing an endoscopic endonasal transsphenoidal approach, where we directly puncture the venous pouch under both stereotactic guidance and endoscopic visualization, thereby completely embolizing a pdAVF with no alternate access (video 1). neurintsurg;15/10/1055/V1F1V1Video 1Technical video demonstrates the complete embolization of a pdAVF using an endoscopic endonasal transsphenoidal approach., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Metal halide perovskite semiconductors have shown significant potential for use in photovoltaic (PV) devices. While fabrication of perovskite thin films can be achieved through a variety of techniques, thermal vapor deposition is particularly promising, allowing for high-throughput fabrication. However, the ability to control the nucleation and growth of these materials, particularly at the charge-transport layer/perovskite interface, is critical to unlocking the full potential of vapor-deposited perovskite PV. In this study, we explore the use of a templating layer to control the growth of coevaporated perovskite films and find that such templating leads to highly oriented films with identical morphology, crystal structure, and optoelectronic properties independent of the underlying layers. Solar cells incorporating templated FA 0.9 Cs 0.1 PbI 3- x Cl x show marked improvements with steady-state power conversion efficiency over 19.8%. Our findings provide a straightforward and reproducible method of controlling the charge-transport layer/coevaporated perovskite interface, further clearing the path toward large-scale fabrication of efficient PV devices., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: In gastric cancer (GC) patients, metastatic progression through the lymphatic, hematogenous, peritoneal, and ovarian routes, is the ultimate cause of death. However, the genomic and evolutionary characteristics of metastatic GC have not been widely evaluated., Methods: Whole-exome sequencing data were analyzed for 99 primary and paired metastatic gastric cancers from 15 patients who underwent gastrectomy and metastasectomy., Results: Hematogenous metastatic tumors were associated with increased chromosomal instability and de novo gain/amplification in cancer driver genes, whereas peritoneal/ovarian metastasis was linked to sustained chromosomal stability and de novo somatic mutations in driver genes. The genomic distance of the hematogenous and peritoneal metastatic tumors was found to be closer to the primary tumors than lymph node (LN) metastasis, while ovarian metastasis was closer to LN and peritoneal metastasis than the primary tumor. Two migration patterns for metastatic GCs were identified; branched and diaspora. Both molecular subtypes of the metastatic tumors, rather than the primary tumor, and their migration patterns were related to patient survival., Conclusions: Genomic characteristics of metastatic gastric cancer is distinctive by routes and associated with patients' prognosis along with genomic evolution pattenrs, indicating that both primary and metastatic gastric cancers require genomic evaluation., (© 2023. The Author(s).)

Accuracy of acceleromyography (AMG) is not be comparable to that of mechanomyography or electromyography (EMG). In particular, the prone position may reduce the accuracy and feasibility of AMG. We developed a new device based on wrist brace to allow free thumb movement and fix the other parts of the hand and wrist. We aimed to test whether the brace applied to the AMG would increase precision of AMG and agreement with the EMG in the prone position. Fifty-seven patients, undergoing lumbar surgery under general anesthesia, were randomly assigned to groups to which AMG was applied with or without (no) brace (29 in group B vs. 28 in group NB). EMG was performed in the contralateral arm. Repeatability coefficients of the first twitch height (T1) and train-of-four (TOF) ratio were assessed from nine consecutive measurements during spontaneous recovery from rocuronium-induced neuromuscular block and the AMGs of the two groups were compared in prone position. The agreement between AMG and EMG in each group was assessed using the Bland-Altman method. In group B, the repeatability coefficient of T1 was significantly lower during the recovery to T1 of 25% and TOF ratio of 0.9 (P = 0.017 and 0.033, respectively), indicating higher precision. The mean differences of bias (95% limits of agreement) between AMG and EMG in TOF ratio of 0.9 were 6.839 (- 26.54 to 40.22) in group NB and 3.922 (- 21.83 to 29.67) in group B. The wide limits of agreement in group NB was slightly narrowed in group B but without significance. Trial registration: registered on the UMIN Clinical Trials Registry in August 2020 (UMIN000041310)., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Agarobiose (AB; d-galactose-β-1,4-AHG), produced by one-step acid hydrolysis of agarose of red seaweed, is considered a promising cosmetic ingredient due to its skin-moisturizing activity. In this study, the use of AB as a cosmetic ingredient was found to be hampered due to its instability at high temperature and alkaline pH. Therefore, to increase the chemical stability of AB, we devised a novel process to synthesize ethyl-agarobioside (ethyl-AB) from the acid-catalyzed alcoholysis of agarose. This process mimics the generation of ethyl α-glucoside and glyceryl α-glucoside by alcoholysis in the presence of ethanol and glycerol during the traditional Japanese sake-brewing process. Ethyl-AB also showed in vitro skin-moisturizing activity similar to that of AB, but showed higher thermal and pH stability than AB. This is the first report of ethyl-AB, a novel compound produced from red seaweed, as a functional cosmetic ingredient with high chemical stability.

This study identified trends in hydroxychloroquine (HCQ) prescription and retinopathy screening in patients with systemic lupus erythematosus (SLE) according to clinical practice guidelines to minimise the risk of HCQ retinopathy. We used data from patients diagnosed with SLE between 2004 and 2019 from the National Health Insurance Service in Korea. To assess trends of daily dose per actual body weight (ABW), we performed an interrupted time-series analysis and identified effects after revision of guidelines. Among 38,973 patients with SLE, 28,415 (72.9%) were prescribed HCQ from 2004 to 2019. The proportion of patients using HCQ among SLE patients was 63% in 2004 and increased to 76% in 2019. The median daily dose per ABW for HCQ users decreased from 5.88 mg/kg in 2004 to 3.98 mg/kg in 2019, and from 5.45 mg/kg in 2005 to 4.17 mg/kg in 2019 for HCQ new users. The annual implementation rate of screening tests among HCQ new users increased from 3.5% in 2006 to 22.5% in 2019. Study results indicated that HCQ dosing management was adequate based on the revised guidelines. Although the implementation rate of retinal screening has increased, it is necessary to enhance awareness of retinal screening in clinical settings., (© 2023. The Author(s).)

The mesenchymal cancer phenotype is known to be clinically related to treatment resistance and a poor prognosis. We identified gene signature-based molecular subtypes of gastric cancer (GC, n = 547) based on transcriptome data and validated their prognostic and predictive utility in multiple external cohorts. We subsequently examined their associations with tumor microenvironment (TME) features by employing cellular deconvolution methods and sequencing isolated GC populations. We further performed spatial transcriptomics analysis and immunohistochemistry, demonstrating the presence of GC cells in a partial epithelial-mesenchymal transition state. We performed network and pharmacogenomic database analyses to identify TGF-β signaling as a driver pathway and, thus, a therapeutic target. We further validated its expression in tumor cells in preclinical models and a single-cell dataset. Finally, we demonstrated that inhibition of TGF-β signaling negated mesenchymal/stem-like behavior and therapy resistance in GC cell lines and mouse xenograft models. In summary, we show that the mesenchymal GC phenotype could be driven by epithelial cancer cell-intrinsic TGF-β signaling and propose therapeutic strategies based on targeting the tumor-intrinsic mesenchymal reprogramming of medically intractable GC., (© 2023. The Author(s).)

Arachnoid cysts of the fourth ventricle are rarely reported. Management options include CSF diversion, cyst fenestration, or cyst excision. Fenestration can be done via open microsurgical technique or endoscopically with or without simultaneous third ventriculostomy; and both rigid and flexible endoscopy have been used successfully. However, application of this treatment modality in pediatric patients is not well described. Therefore, to their knowledge, the authors report the first successful treatment of a fourth ventricular arachnoid cyst with a single frontal burr hole entry point for third ventriculostomy and fourth ventricular arachnoid cyst fenestration performed using flexible neuroendoscopy. The patient was a 13-month-old boy presenting with progressive macrocephaly. The authors review their technique, discuss special considerations when using this approach, and include an annotated intraoperative video for demonstration to help instruct and guide management. The authors demonstrate with an example that a single frontal burr hole entry point for flexible endoscopic third ventriculostomy and navigation through a dilated cerebral aqueduct for fourth ventricular arachnoid cyst fenestration is a viable treatment for symptomatic fourth ventricular arachnoid cysts in children.

Bioactive peptides (BPs) are protein fragments that benefit human health. To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs., (© 2022 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

This study aimed to identify factors influencing disaster preparedness capability, measure and compare the relative importance of evaluation indicators of preparedness capability in a rainstorm disaster, and analyze the impact of these factors on disaster preparedness so as to improve disaster preparedness capability. The evaluation model was proposed by constructing the target level (the first level) as an indicator system; this was divided into four indicators (the second level): planning, organization, equipment, and education and exercise, and 14 tertiary evaluation indicators (the third level). The validity of the evaluation index system was demonstrated, and the weight of each level was calculated using the Analytic Hierarchical Process and expert survey methods, taking the example of the Zhengzhou "7.20" rainstorm to conduct an empirical analysis of the proposed model. The weak points of disaster preparedness capability were identified. The empirical analysis revealed that organization scored the highest, followed by planning, equipment, and education and exercise, indicating the lack of disaster management equipment and resources, disaster management training, and exercise and public emergency safety education. These results will help in future decision-making, as they provide a clear understanding of what needs to be done to improve disaster preparedness capability., Competing Interests: The authors declare no conflicts of interest.

A structural protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), nucleocapsid (N) protein is phosphorylated by glycogen synthase kinase (GSK)-3 on the serine/arginine (SR) rich motif located in disordered regions. Although phosphorylation by GSK-3β constitutes a critical event for viral replication, the molecular mechanism underlying N phosphorylation is not well understood. In this study, we found the putative alpha-helix L/FxxxL/AxxRL motif known as the GSK-3 interacting domain (GID), found in many endogenous GSK-3β binding proteins, such as Axins, FRATs, WWOX, and GSKIP. Indeed, N interacts with GSK-3β similarly to Axin, and Leu to Glu substitution of the GID abolished the interaction, with loss of N phosphorylation. The N phosphorylation is also required for its structural loading in a virus-like particle (VLP). Compared to other coronaviruses, N of Sarbecovirus lineage including bat RaTG13 harbors a CDK1-primed phosphorylation site and Gly-rich linker for enhanced phosphorylation by GSK-3β. Furthermore, we found that the S202R mutant found in Delta and R203K/G204R mutant found in the Omicron variant allow increased abundance and hyper-phosphorylation of N. Our observations suggest that GID and mutations for increased phosphorylation in N may have contributed to the evolution of variants.

Objective: Genetic alterations are increasingly recognized as etiologic factors linked to the pathogenesis and development of cerebrovascular anomalies. Their identification allows for advanced screening and targeted therapeutic approaches. The authors aimed to describe the role of a collaborative approach to care and genetic testing in pediatric patients with neurovascular anomalies, with the objectives of identifying what genetic testing recommendations were made, the yield of genetic testing, and the implications for familial screening and management at present and in the future., Methods: The authors performed a descriptive retrospective cohort study examining pediatric patients genetically screened through the Pediatric Neurovascular Program of a single treatment center. Patients 18 years of age and younger with neurovascular anomalies, diagnosed radiographically or histopathologically, were evaluated for germline genetic testing. Patient demographic data and germline genetic testing and recommendation, clinical, treatment, and outcome data were collected and analyzed., Results: Sixty patients were included; 29 (47.5%) were female. The mean age at consultation was 11.0 ± 4.9 years. Diagnoses included cerebral arteriovenous malformations (AVMs) (n = 23), cerebral cavernous malformations (n = 19), non-neurofibromatosis/non-sickle cell moyamoya (n = 8), diffuse cerebral proliferative angiopathy, and megalencephaly-capillary malformation. Of the 56 patients recommended to have genetic testing, 40 completed it. Genetic alterations were found in 13 (23%) patients. Four patients with AVMs had RASA1, GDF2, and ACVRL1 mutations. Four patients with cavernous malformations had Krit1 mutations. One with moyamoya disease had an RNF213 mutation. Three patients with megalencephaly-capillary malformation had PIK3CA mutations, and 1 patient with a cavernous sinus lesion had an MED12 mutation. The majority of AVM patients were treated surgically. Patients with diffuse cerebral proliferative angiopathy were treated medically with sirolimus. At-risk relatives of 3 patients positive for genetic anomalies had also been tested., Conclusions: This study demonstrates a role for exploring genetic alterations in the identification and treatment of pediatric neurovascular disease pathogenesis. Germline genetic mutations were found in almost one-quarter of the patients screened in this study, results that helped to identify medically targeted treatment modalities for some pediatric neurovascular patients. Insight into the genetic etiology of vascular anomalies may provide broader clinical implications for risk assessment, family screening, follow-up surveillance, and medical management.

The intratumoral accumulation of nanomedicine has been considered a passive process, referred to as the enhanced permeability and retention effect. Recent studies have suggested that the tumor uptake of nanomedicines follows an energy-dependent pathway rather than being a passive process. Herein, to explore the factor candidates that are associated with nanomedicine tumor uptake, a molecular marker identification platform is developed by integrating microscopic fluorescence images of a nanomedicine distribution with spatial transcriptomics information. When this approach is applied to PEGylated liposomes, molecular markers related to hypoxia, glycolysis, and apoptosis can be identified as being related to the intratumoral distribution of the nanomedicine. It is expected that the method can be applied to explain the distribution of a wide range of nanomedicines and that the data obtained from this analysis can enhance the precise utilization of nanomedicines., (© 2022 Wiley-VCH GmbH.)

The Woven EndoBridge (WEB) device was approved by the U.S. FDA for its excellent angiographic occlusion of intracranial aneurysms and high safety profile, based on the landmark WEB-IT (WEB Intrasaccular Therapy) trial. There remains, however, a few cases of aneurysm recurrence that necessitate retreatment after the initial WEB procedure. In this technical video, the authors present the case of a middle-aged patient who showed significant basilar apex aneurysm recurrence and growth along with device compaction that required retreatment. Various aspects of treating aneurysms with a prior WEB device, including procedural technique, are discussed. The video can be found here: https://stream.cadmore.media/r10.3171/2022.7.FOCVID21152., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication.The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication., (© 2022, The Authors.)

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to have high infectivity and is more likely to evade vaccine immunity. However, booster vaccination is expected to strengthen cross-reactive immunity, thereby increasing the vaccine effectiveness (VE). This study aimed to evaluate the relative VE of the 3-dose (booster) vaccination compared with the 2-dose primary series vaccination in healthcare workers during omicron variant-dominant periods. During the omicron-dominant period from February 1, 2022 to February 28, 2022, a 1:1 matched case-control study was conducted. Healthcare workers with positive SARS-CoV-2 test results were classified as positive cases, whereas those with negative results served as controls. Compared with the 2-dose primary series vaccination, booster vaccination with mRNA vaccine showed moderate VE (53.1%). However, in multivariate analysis including the time elapsed after vaccination, the significant VE disappeared, reflecting the impact of recent vaccination rather than the third dose itself., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.

Cancer was thought to be caused solely by genetic mutations in oncogenes and tumor suppressor genes. In the last 35 years, however, epigenetic changes have been increasingly recognized as another primary driver of carcinogenesis and cancer progression. Epigenetic deregulation in cancer often includes mutations and/or aberrant expression of chromatin-modifying enzymes, their associated proteins, and even non-coding RNAs, which can alter chromatin structure and dynamics. This leads to changes in gene expression that ultimately contribute to the emergence and evolution of cancer cells. Studies of the deregulation of chromatin modifiers in cancer cells have reshaped the way we approach cancer and guided the development of novel anticancer therapeutics that target epigenetic factors. There remain, however, a number of unanswered questions in this field that are the focus of present research. Areas of particular interest include the actions of emerging classes of epigenetic regulators of carcinogenesis and the tumor microenvironment, as well as epigenetic tumor heterogeneity. In this review, we discuss past findings on epigenetic mechanisms of cancer, current trends in the field of cancer epigenetics, and the directions of future research that may lead to the identification of new prognostic markers for cancer and the development of more effective anticancer therapeutics., (Copyright © 2021. Published by Elsevier Ltd.)

Food-derived bioactive peptides (BPs) have received considerable attention as postbiotics for human gut health. Here we used a genomics-based semirational approach to expand the postbiotic potential of collagen peptides (CPs) produced from probiotic fermentation. In silico digestion revealed distinct BPs embedded in fish collagen in a protease-dependent manner. Anaerobic digestion of collagen by representative Lactobacillaceae species revealed differential substrate utilization and collagen degradation patterns. Nanoliquid chromatography-mass spectrometry analysis of CPs showed that each species exhibited different cleavage patterns and unique peptide profiles. Remarkably, the 1-10 kDa CPs produced by Lacticaseibacillus paracasei showed agonistic activities toward G protein-coupled receptor 35 (GPR35). These CPs could repair intestinal epithelium through the GPR35-mediated extracellular signal-regulated protein kinase (ERK) 1/2 signaling pathway, suggesting that probiotic-aided collagen hydrolysates can serve as postbiotics for host-microbe interactions. Therefore, this study provides an effective strategy for the rapid screening of CPs for gut health in the gastrointestinal tract.

Background: Mucinous gastric adenocarcinoma (MGC) is a rare but distinctive histologic subtype of gastric cancer (GC). The clinico-pathologic and genomic characteristics of MGC have not been well evaluated., Methods: We collected individual data from five cohorts targeting the microsatellite instability (MSI) of GC (n = 5089) to evaluate the clinico-pathologic characteristics of MGC. In addition, public genomic databases were used for genomic analysis. The characteristics of MGC were compared with those of non-mucinous GC (NMGC)., Results: MGC (n = 158, 3.1%) showed distinctive characteristics in terms of age, sex, and TNM stage compared to NMGC (n = 4931). MGC was frequently associated with MSI-high (OR: 2.24, 95% confidence interval [CI] 1.44-3.40, p < 0.001), while mutually exclusive to the Epstein-Barr virus type. The prognosis of MGC was better than that of NMGC (adj.HR: 0.731, 95% CI 0.556-0.962, p = 0.025). There was no clear benefit from postoperative chemotherapy in MGC. TP53 was the main driver mutation in the MGC without recurrent variants. MGC was related to high expression of GPR120 and B3GNT6 and moderate regulation of epithelial-mesenchymal transition (EMT)-up signature with a high EMT-down signature, and those characteristics was related to favorable prognosis of GC (log-rank p = 0.044, p < 0.001, p < 0.001, respectively). MSI-H of MGC was associated with low cancer-associate fibroblasts but high CD274 (PD-L1) expression compared to microsatellite stable MGC, suggesting that immune checkpoint inhibitors may be useful for the MSI-H of MGC., Conclusion: MGC could be a surrogate for performing MSI but not the EBV test in GC. Further, its genetic characteristics lead to a favorable prognosis for MGC., (© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease. Environmental sanitization, modern lifestyles, advanced medicines, ethnic origins, host genetics and immune systems, mucosal barrier function, and the gut microbiota have been delineated to explain how they cause mucosal inflammation. However, the pathogenesis of IBD and its therapeutic targets remain elusive. Recent studies have highlighted the importance of the human gut microbiota in health and disease, suggesting that the pathogenesis of IBD is highly associated with imbalances of the gut microbiota or alterations of epithelial barrier function in the gastrointestinal (GI) tract. Moreover, diet-induced alterations of the gut microbiota in the GI tract modulate immune responses and perturb metabolic homeostasis. This review summarizes recent findings on IBD and its association with diet-induced changes in the gut microbiota; furthermore, it discusses how diets can modulate host gut microbes and immune systems, potentiating the impact of personalized diets on therapeutic targets for IBD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

This study empirically analyzes how corporate social responsibility (CSR) performance feedback impacts CSR performance, focusing on the performance feedback perspective of behavioral theory of the firm (BTOF). By performing generalized least squares (GLS) regression analysis based on Korean company data from 2012 to 2019, we presented evidence that positive social and historical performance feedback had a positive effect on CSR performance. Our results provide evidence that firms with higher social and historical CSR performance than CSR aspiration may have higher CSR performance than those that do not., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee and Yang.)

Objectives: The objective of this study was to evaluate the efficacy of cell therapy using human amniotic epithelial stem cells (hAESCs) for the treatment of premature rupture of membranes (PROM) in vitro., Design: Using the amniotic pore culture technique (APCT), we mimicked the environment of PROM in vitro, thus enabling the observation of the healing process of hAESC-treated amniotic membranes., Materials: Amniotic membrane samples were collected from placentas of pregnant women who underwent elective cesarean sections. APCT model and isolated hAESCs were used in this study. All patients who participated in this study provided their written informed consent prior to the commencement of the study., Settings: To create the APCT model in vitro, isolated amniotic membranes were punched to create 5 mm diameter circles and re-punched to form a 1-mm pore at the center. Membranes were cultured in α-minimal essential medium, and the hAESCs were collected and cultured as well. Subsequently, the APCT models were divided into two groups: hAESC treated and control., Methods: Within the culture period, pore sizes were calculated to evaluate the degree of tissue regeneration in both groups. We then evaluated the histology, cell density, and epithelial thickness of the regenerated tissues. Statistical analyses were performed using SPSS software ver. 20.0 (IBM, Armonk, NY, USA) with repeated-measures one-way analysis of variance or paired samples t test. The significance level was set at p < 0.05., Results: As per the evaluation of the APCT model in vitro, the pore size in the hAESC-treated group reduced by 62.2% on day 6 (62.2 ± 0.19, n = 24), whereas in the control group, it shrank by only 36.8% (p < 0.05) (36.8 ± 0.19, n = 24). Furthermore, the epithelial thickness in the amniotic epithelial stem cell-treated group (10.08 ± 1.26 μm, n = 8) was significantly higher than that in the control group (5.87 ± 0.94 μm, n = 8). Cell density in the regenerated tissue in the amniotic epithelial stem cell-treated group (57 ± 2.77, n = 8) was significantly higher than that in the control group (49 ± 2.23, n = 8)., Limitations: In this study, we did not explore the molecular mechanisms by which hAESCs participate in membrane healing in the APCT model. Although our results showed a significant difference, this difference was not too obvious. Therefore, further research on the mechanisms of hAESCs is needed, with more amniotic tissues and APCT samples being tested., Conclusions: We developed an APCT model to investigate the PROM conditions in vitro. By implanting donor hAESCs in the pores of the APCT model, we observed that hAESCs seeding accelerated pore healing in vitro. Thus, hAESCs may be a valuable source of cells for cell therapies in regenerative medicine., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Since the outbreak of the novel coronavirus disease (COVID-19), the government has provided infection-control guidelines to prevent the spread of the virus. The authors of this study examined the structure (causal relationship) of factors that influence public behavior toward COVID-19 and verified the effect of public empathy with infection-control guidelines in each structure. Data were collected using a self-administered questionnaire survey from 211 Korean adults. The results showed that (1) the perceived susceptibility and severity of economic damage had a positive effect on infection-prevention attitudes and infection-prevention attitudes had a positive effect on infection-prevention behaviors; (2) the perceived severity of economic damage had a positive effect on infection-prevention attitudes; and (3) public empathy with infection-control guidelines positively moderated the effect of the perceived severity of economic damage on infection-prevention behaviors and that of perceived susceptibility on infection-prevention attitudes. Accordingly, the authors of this study present the following three suggestions to prevent the spread of an infectious disease: engage in risk communication focused on a potential virus infection and cooperation, make multifaceted efforts to increase public empathy with infection-control guidelines, and implement measures to alleviate or reduce economic damage to the public in a viral pandemic.

Lately, there has been a rapid increase in the use of software-based deep learning neural networks (S-DNN) for the analysis of unstructured data consumption. For implementation of the S-DNN, synapse-device-based hardware DNN (H-DNN) has been proposed as an alternative to typical Von-Neumann structural computing systems. In the H-DNN, various numerical values such as the synaptic weight, activation function, and etc., have to be realized through electrical device or circuit. Among them, the synaptic weight that should have both positive and negative numerical values needs to be implemented in a simpler way. Because the synaptic weight has been expressed by conductance value of the synapse device, it always has a positive value. Therefore, typically, a pair of synapse devices is required to realize the negative weight values, which leads to additional hardware resources such as more devices, higher power consumption, larger area, and increased circuit complexity. Herein, we propose an alternative simpler method to realize the negative weight (named weight shifter) and its hardware implementation. To demonstrate the weight shifter, we investigated its theoretical, numerical, and circuit-related aspects, following which the H-DNN circuit was successfully implemented on a printed circuit board., (© 2021. The Author(s).)

The photoelectrochemical performance of a co-doped hematite photoanode might be hindered due to the unintentionally diffused Sn from a fluorine-doped tin oxide (FTO) substrate during the high-temperature annealing process by providing an increased number of recombination centers and structural disorder. We employed a two-step annealing process to manipulate the Sn concentration in co-doped hematite. The Sn content [Sn/(Sn + Fe)] of a two-step annealing sample decreased to 1.8 from 6.9% of a one-step annealing sample. Si and Sn co-doped hematite with the reduced Sn content exhibited less structural disorder and improved charge transport ability to achieve a 3.0 mA cm -2 photocurrent density at 1.23 V RHE , which was 1.3-fold higher than that of the reference Si and Sn co-doped Fe 2 O 3 (2.3 mA cm -2 ). By decorating with the efficient co-catalyst NiFe(OH) x , a maximum photocurrent density of 3.57 mA cm -2 was achieved. We further confirmed that the high charging potential and poor cyclability of the zinc-air battery could be dramatically improved by assembling the optimized, stable, and low-cost hematite photocatalyst with excellent OER performance as a substitute for expensive Ir/C in the solar-assisted chargeable battery. This study demonstrates the significance of manipulating the unintentionally diffused Sn content diffused from FTO to maximize the OER performance of the co-doped hematite.

Castration-resistant prostate cancer (CRPC) is a highly aggressive and advanced prostate cancer that is currently incurable with conventional therapies. The recurrence and chemotherapy-resistant properties of CRPC are attributed to prostate cancer stem cells (CSCs). On the other hand, the factors regulating the prostate CSC-like properties have not been studied extensively. Previously, ubiquitin C-terminal hydrolase-L1 (UCH-L1) and ubiquitin C-terminal hydrolase-L3 (UCH-L3) were reported to be involved in prostate cancer cell progression through the epithelial-to-mesenchymal transition (EMT) regulation. Here, the differential regulation on the CSC-like properties by UCH-L1 and UCH-L3 were identified in prostate cancer cells. The CSC-like characteristics, such as the expression of pluripotency markers, chemoresistance, and sphere-forming ability, were promoted by UCH-L1, whereas those were repressed by UCH-L3. Moreover, the modulation of CSC-like properties by UCH-L1 and UCH-L3 was through the PI3 K/Akt signaling pathway. The CSC-like properties induced by UCH-L1 overexpression or UCH-L3 depletion were suppressed by the PI3 K/Akt pathway inhibitor. In conclusion, UCH-L1 and UCH-L3 are novel regulators of the CSC-like properties and shed light on new therapeutic strategies to overcome CSCs in prostate cancers., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

This study sought to evaluate DNA damage and repair in porcine postovulatory aged oocytes. The DNA damage response, which was assessed by H2A.X expression, increased in porcine aged oocytes over time. However, the aged oocytes exhibited a significant decrease in the expression of RAD51, which reflects the DNA damage repair capacity. Further experiments suggested that the DNA repair ability was suppressed by the downregulation of genes involved in the homologous recombination (HR) and nonhomologous end-joining (NHEJ) pathways. The expression levels of the cell cycle checkpoint genes, CHEK1 and CHEK2 , were upregulated in porcine aged oocytes in response to induced DNA damage. Immunofluorescence results revealed that the expression level of H3K79me2 was significantly lower in porcine aged oocytes than in control oocytes. In addition, embryo quality was significantly reduced in aged oocytes, as assessed by measuring the cell proliferation capacity. Our results provide evidence that DNA damage is increased and the DNA repair ability is suppressed in porcine aged oocytes. These findings increase our understanding of the events that occur during postovulatory oocyte aging., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2021 Korean Society of Animal Science and Technology.)

The deregulation of polypeptide N-acetyl-galactosaminyltransferases (GALNTs) contributes to several cancers, but their roles in lung cancer remain unclear. In this study, we have identified a tumor-suppressing role of GALNT3 in lung cancer. We found that GALNT3 suppressed lung cancer development and progression in both xenograft and syngeneic mouse models. Specifically, GALNT3 suppressed lung cancer initiation by inhibiting the self-renewal of lung cancer cells. More importantly, GALNT3 attenuated lung cancer growth by preventing the creation of a favorable tumor microenvironment (TME), which was attributed to GALNT3's ability to inhibit myeloid-derived suppressor cell (MDSC) infiltration into tumor sites and subsequent angiogenesis. We also identified a GALNT3-regulated gene (GRG) signature and found that lung cancer patients whose tumors exhibit the GRG signature showed more favorable prognoses. Further investigation revealed that GALNT3 suppressed lung cancer cell self-renewal by reducing β-catenin levels, which led to reduced expression of the downstream targets of the WNT pathway. In addition, GALNT3 inhibited MDSC infiltration into tumor sites by suppressing both the TNFR1-NFκB and cMET-pAKT pathways. Specifically, GALNT3 inhibited the nuclear localization of NFκB and the c-MET-induced phosphorylation of AKT. This then led to reduced production of CXCL1, a chemokine required for MDSC recruitment. Finally, we confirmed that the GALNT3-induced inhibition of the TNFR1-NFκB and cMET-pAKT pathways involved the O-GalNAcylation of the TNFR1 and cMET receptors. In summary, we have identified GALNT3 as the first GALNT member capable of suppressing lung cancer and uncovered a novel mechanism by which GALNT3 regulates the TME., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Resveratrol (RES) and oxyresveratrol (OXYRES) are considered and utilized as active ingredients of anti-aging skin cosmetics. However, these compounds are susceptible to oxidative discoloration and unpleasant odor in solutions, limiting their use in cosmetics. Accordingly, RES and OXYRES were chemically modified to acetylated derivatives with enhanced stability, and their anti-aging effect on the skin and detailed molecular mechanism of their acetylated derivatives were investigated. Acetylated RES and OXYRES lost their acetyl group and exerted an inhibitory effect on H 2 O 2 -induced ROS levels in human dermal fibroblast (HDF) cells. In addition, RES, OXYRES, and their acetylated derivatives suppressed UVB-induced matrix metalloproteinase (MMP)-1 expression via inhibition of mitogen-activated protein kinases (MAPKs) and Akt/mTOR signaling pathways. Furthermore, RES, OXYRES, and their acetylated derivatives suppressed type I collagen in TPA-treated HDF cells. Collectively, these results suggest the beneficial effects and underlying molecular mechanisms of RES, OXYRES, and their acetylated derivatives for anti- skin aging applications.

Background: Evidence-based interventions are needed to address the use of stimulants such as methamphetamine as a driver of onward HIV transmission and faster clinical HIV progression among sexual minority men. Prior randomized controlled trials with people living with HIV who use substances indicate that financial incentives provided during contingency management (CM) are effective for achieving short-term reductions in stimulant use and HIV viral load. However, the benefits of CM are often not maintained after financial incentives for behavior change end., Purpose: Data from a recently completed randomized controlled trial with 110 sexual minority men living with HIV who use methamphetamine was leveraged to examine mediators of the efficacy of a positive affect intervention for extending the benefits of CM., Methods: An autoregressive cross-lagged model was fit to determine if reductions in HIV viral load were mediated by intervention-related increases in positive affect and decreases in stimulant use measured in four waves over 15 months., Results: Higher baseline positive affect predicted significantly lower self-reported stimulant use immediately following the 3-month CM intervention period, even after controlling for self-reported stimulant use at baseline. Moreover, decreased stimulant use emerged as an independent predictor of long-term reductions HIV viral load at 15 months, even after adjusting for HIV viral load at baseline and the residual effect of the positive affect intervention., Conclusions: Findings underscore the importance of durable reductions in stimulant use as a primary intervention target that is essential for optimizing the clinical and public health benefits of HIV treatment as prevention., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to investigate the relationship between the concurrent use of benzodiazepines and opioids and the risk of fractures in older patients with chronic non-cancer pain., Methods: Patients with osteoarthritis or low back pain (≥ 65 years of age) included in the Korean National Health Insurance Service-National Sample Cohort database of Korea and with an incident diagnosis of hip, humeral, or forearm fracture between 2011 and 2015 were identified as cases. For each case, four controls were matched for age (within 5 years), sex, and year of cohort entry. We estimated the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for fractures associated with concurrent use of benzodiazepines and opioids using a conditional logistic regression analysis, adjusting for comorbidities and comedications., Results: The aOR (95% CI) for the concurrent use of benzodiazepines and opioids was 1.45 (1.22-1.71), compared with those of non-use within 30 days before the index date. The aOR was 1.65 (1.22-2.23) in patients who were continuously receiving benzodiazepines and were newly initiated with concurrent opioids. The aORs for concurrent use were 1.95 (1.39-2.74) and 1.27 (1.03-1.56) in the case of hip fracture and forearm fracture, respectively., Conclusion: The concurrent use of benzodiazepines and opioids was associated with an increased risk of fractures in older patients with chronic non-cancer pain. Therefore, patients continuously receiving benzodiazepines in whom opioids are newly initiated need careful monitoring, and such combined therapy should be limited to the shortest duration possible., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This paper proposes a method to embed and extract a watermark on a digital hologram using a deep neural network. The entire algorithm for watermarking digital holograms consists of three sub-networks. For the robustness of watermarking, an attack simulation is inserted inside the deep neural network. By including attack simulation and holographic reconstruction in the network, the deep neural network for watermarking can simultaneously train invisibility and robustness. We propose a network training method using hologram and reconstruction. After training the proposed network, we analyze the robustness of each attack and perform re-training according to this result to propose a method to improve the robustness. We quantitatively evaluate the results of robustness against various attacks and show the reliability of the proposed technique.

Along with early-onset cancers, multiple primary cancers (MPCs) are likely resulting from increased genetic susceptibility; however, the associated predisposition genes or prevalence of the pathogenic variants genes in MPC patients are often unknown. We screened 71 patients with MPC of the stomach, colorectal, and endometrium, sequencing 65 cancer predisposition genes. A subset of 19 patients with early-onset MPC of stomach and colorectum were further evaluated for variants in cancer related genes using both normal and tumor whole exome sequencing. Among 71 patients with MPCs, variants classified to be pathogenic were observed in 15 (21.1%) patients and affected Lynch Syndrome (LS) genes: MLH1 (n = 10), MSH6 (n = 2), PMS2 (n = 2), and MSH2 (n = 1). All carriers had tumors with high microsatellite instability and 13 of them (86.7%) were early-onset, consistent with LS. In 19 patients with early-onset MPCs, loss of function (LoF) variants in RECQL5 were more prevalent in non-LS MPC than in matched sporadic cancer patients (OR = 31.6, 2.73-1700.6, p = 0.001). Additionally, there were high-confidence LoF variants at FANCG and CASP8 in two patients accompanied by somatic loss of heterozygosity in tumor, respectively. The results suggest that genetic screening should be considered for synchronous cancers and metachronous MPCs of the LS tumor spectrum, particularly in early-onset. Susceptibility variants in non-LS genes for MPC patients may exist, but evidence for their role is more elusive than for LS patients., (© 2021. The Author(s).)