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David Baunoch,1,2 Natalie Luke,2 Dakun Wang,3 Annah Vollstedt,4 Xinhua Zhao,5 Dicken SC Ko,6 Shuguang Huang,5 Patrick Cacdac,2 Larry T Sirls4 1Research/Development, Pathnostics, Irvine, CA, USA; 2Clinical Affairs, Pathnostics, Irvine, CA, USA; 3Medical Writing, Stat4ward, Pittsburgh, PA, USA; 4Women’s Urology and Pelvic Health Center, Beaumont Hospital, Royal Oak, MI, USA; 5Statistics, Stat4ward, Pittsburgh, PA, USA; 6Department of Bio Med Surgery, Warren Alpert Medical School of Brown University, Providence, RI, USACorrespondence: David Baunoch Email dbaunoch@pathnostics.comPurpose: Studies have shown that multiple genes influence antibiotic susceptibility, but the relationship between genotypic and phenotypic antibiotic susceptibility is unclear. We sought to analyze the concordance between the presence of antibiotic resistance (ABR) genes and antibiotic susceptibility results in urine samples collected from patients with symptomatic urinary tract infection (UTI).Patients and Methods: Urine samples were collected from patients presenting to 37 geographically disparate urology clinics across the United States from July 2018 to February 2019. Multiplex polymerase chain reaction was used to detect 27 ABR genes. In samples containing at least one culturable organism at a concentration of ≥ 104 cells per mL, pooled antibiotic susceptibility testing (P-AST), which involves simultaneous growing all detected bacteria together in the presence of antibiotic and then measure susceptibility, was performed against 14 antibiotics. The concordance rate between the ABR genes and the P-AST results was generated for the overall group. The concordance rates for each antibiotic between monomicrobial and polymicrobial infection were compared using chi-square test.Results: Results from ABR gene detection and P-AST of urine samples from 1155 patients were included in the concordance analysis. Overall, there was a 60% concordance between the presence or absence of ABR genes and corresponding antimicrobial susceptibility with a range of 49– 78% across antibiotic classes. Vancomycin, meropenem, and piperacillin/tazobactam showed significantly lower concordance rates in polymicrobial infections than in monomicrobial infections.Conclusion: Given the 40% discordance rate, the detection of ABR genes alone may not provide reliable data to make informed clinical decisions in UTI management. However, when used in conjunction with susceptibility testing, ABR gene data can offer valuable clinical information for antibiotic stewardship.Keywords: urinary tract infection, antibiotic resistance, antibiotic resistance genes, bacteria, culture, antibiotic susceptibility test, polymerase chain reaction

Background: Chronic widespread pain (CWP) affects approximately 10% of the adult population globally, causing significant physical and psychological distress. Micronutrients, such as iron, copper, zinc, and magnesium, are essential in various physiological functions, and their imbalances may impact pain perception and chronic pain conditions. Methods : This study used Mendelian randomization (MR) to investigate the causal relationships between micronutrient levels and CWP. Data were obtained from genome-wide association studies (GWASs) for iron, copper, zinc, and magnesium, and CWP data were sourced from large-scale GWASs with 461,857 European participants. Genetic variants were used as instrumental variables to infer causal relationships, minimizing confounding factors. Results : MR analysis revealed a significant association between higher iron levels and an increased risk of CWP (IVW, OR 1.01, 95% CI: 1.00-1.01, p = 0.029). This finding was supported by the weighted median and MR-Egger methods. No significant associations were found for copper, zinc, and magnesium levels. Conclusions : These results suggest that iron levels may influence pain perception and chronic pain conditions. Balanced iron levels are crucial for managing chronic pain. Regular monitoring and personalized treatment plans could benefit individuals with CWP. Further research is needed to understand the mechanisms linking micronutrient levels to chronic pain and to develop targeted therapeutic interventions.

Obesity is a major public health concern associated with a higher risk of various comorbidities. Some studies have explored the impact of obesity on cognitive function and, conversely, how lower intelligence might increase the risk of later obesity. The aim of this study is to analyze a complex relationship between body mass index (BMI) and intelligence quotient (IQ), employing a comprehensive approach, including a systematic review, meta-analysis, and Mendelian randomization (MR). We extracted the data from Medline and Embase to identify relevant studies published since June 22, 2009. MR analysis relied on genetic databases such as the Genome-Wide Association Study (GWAS) and the Genetic Investigation of Anthropometric Traits (GIANT) to explore potential causal relationships. The systematic review and meta-analysis encompassed 34 and 17 studies, respectively. They revealed a substantial correlation between obesity and reduced IQ, particularly notable among school-age children (mean difference -5.26; 95% CI: -7.44 to -3.09). Notably, within the IQ subgroup, verbal IQ also exhibited a significant association with a mean difference of -7.73 (95% CI: -14.70 to -0.77) in school-age children. In contrast, the MR did not unveil a significant causal relationship between BMI and IQ, both in childhood and adulthood. This comprehensive analysis underscores a significant correlation between BMI and IQ, particularly in school-age children. However, the MR analysis implies a potentially weaker causal relationship. Future large-scale cohort studies should address potential confounding factors to provide further insights into the BMI-IQ relationship., (© 2024 World Obesity Federation.)

This review aimed to highlight the pivotal role of Mendelian randomization (MR) in advancing atherosclerotic cardiovascular disease (ASCVD) research-a field often hindered by the complexities and limitations of traditional studies. MR, which uses genetic variants as instrumental variables, provides a robust mechanism for inferring causality, offering insights untainted by the confounding factors and biases often prevalent in observational and randomized controlled trials. We explored the significant contributions of MR for elucidating the causal relationship between low-density lipoprotein cholesterol and ASCVD, and analyzed its assumptions and methodological nuances. We discussed issues surrounding instrumental variable selection, pleiotropy, and ethical considerations, in an effort to offer a balanced and insightful analysis. We highlighted the promising integration of MR with emerging technologies and global data sharing, as well as its potential to drive personalized medicine. This review provided a concise yet comprehensive journey into MR's transformative impact on ASCVD research, offering a blend of current insights and challenges, in addition to future prospects. We aimed to serve a valuable resource for those seeking to navigate the intricate pathways of causality and intervention in ASCVD, to aid the development of enhanced understanding and targeted treatment strategies in the future., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (© 2024 The Korean Society of Lipid and Atherosclerosis.)

Background: The escalating utilization of assisted reproductive technology (ART) in response to global infertility rates has spurred research into its complications. Short-term and long-term outcomes have been extensively studied, particularly the neurological concerns surrounding attention-deficit/hyperactivity disorder (ADHD) among ART-conceived children. This study aims investigate the association between ART and ADHD., Methods: Medline, Embase, Scopus, and Web of Science databases were searched through April 4, 2023. Cohort, case-control, and cross-sectional studies were eligible for inclusion. primary summary measures included the unadjusted relative risk (RR) and adjusted hazard ratio (HR) with 95 % confidence intervals. Both fixed-effects and random-effects models were utilized for meta-analysis data pooling to determine the overall effect size. The onset of ADHD in children conceived through ART compared to those conceived naturally., Results: The systematic search yielded 8 studies with 10,176,148 individuals included in the meta-analysis. The meta-analysis revealed a pooled RR of 0.93 (0.68-1.26) for cohort studies and a pooled RR of 0.97 (0.41-2.29) for cross-sectional studies, along with a pooled HR of 1.08 (1.03-1.13) for ADHD in the ART group compared to the non-ART group., Conclusion: While this study identifies some potential association between ART and ADHD, the limited effect size and inherent heterogeneity underscore the need for cautious interpretation., Competing Interests: Declaration of Competing Interest All Authors have none to declare, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Avian pathogenic Escherichia coli (APEC) causes enormous economic losses and is a primary contributor to the emergence of multidrug resistance (MDR)-related problems in the poultry industry. Bacteriophage (phage) therapy has been successful in controlling MDR, but phage-resistant variants have rapidly emerged through the horizontal transmission of diverse phage defense systems carried on mobile genetic elements. Consequently, while multiple phage cocktails are recommended for phage therapy, there is a growing need to explore simpler and more cost-effective phage treatment alternatives. In this study, we characterized two novel O78-specific APEC phages, φWAO78-1 and φHAO78-1, in terms of their morphology, genome, physicochemical stability and growth kinetics. Additionally, we assessed the susceptibility of thirty-two O78 APEC strains to these phages. We analyzed the roles of highly susceptible cells in intestinal settlement and fecal shedding (susceptible cell-assisted intestinal settlement and shedding, SAIS) of phages in chickens via coinoculation with phages. Furthermore, we evaluated a new strategy, susceptible cell-assisted resistant cell killing (SARK), by comparing phage susceptibility between resistant cells alone and a mixture of resistant and highly susceptible cells in vitro. As expected, high proportions of O78 APEC strains had already acquired multiple phage defense systems, exhibiting considerable resistance to φWAO78-1 and φHAO78-1. Coinoculation of highly susceptible cells with phages prolonged phage shedding in feces, and the coexistence of susceptible cells markedly increased the phage susceptibility of resistant cells. Therefore, the SAIS and SARK strategies were demonstrated to be promising both in vivo and in vitro., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hyuk-Joon Kwon reports financial support was provided by GeNiner Inc. Hyuk-Joon Kwon reports financial support was provided by The National Research Foundation of Korea (NRF). Eun-Jin Ha reports financial support was provided by GeNiner Inc. Eun-Jin Ha reports financial support was provided by The National Research Foundation of Korea (NRF). Seung-Min Hong reports financial support was provided by GeNiner Inc. Seung-Min Hong reports financial support was provided by The National Research Foundation of Korea (NRF). Hyuk-Joon Kwon has patent #10-2011-0030062 issued to Seoul National University R&DB Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Epilepsy, characterized by recurrent unprovoked seizures, poses significant challenges to affected individuals globally. While several established risk factors for epilepsy exist, the association with cigarette smoking remains debated. This study aims to conduct systematic review and meta-analysis to elucidate the potential association between smoking and the likelihood of epilepsy., Methods: The search was performed on March 31st, 2023, using the Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included cohort, cross-sectional, and case-control studies in our meta-analysis, conducting subgroup analyses based on smoking history, sex, and epilepsy type to yield specific insights., Results: We identified 2550 studies, of which 17 studies were finally included in this study. The pooled odds ratio of epilepsy was 1.14 (0.96-1.36) in smokers compared to non-smokers. In current smokers compared to non-smokers, the odds ratio was 1.46 (1.13-1.89), while, in former smokers compared to non-smokers, the odds ratio was 1.14 (0.83-1.56)., Conclusions: While the overall association between smoking and epilepsy did not reach statistical significance, a notable association was found among current smokers. The study emphasizes the importance of smoking cessation as a potential preventive measure against epilepsy, especially given the proconvulsive effects of nicotine. Future research should address limitations and explore specific clinical scenarios to enhance our understanding of the complex relationship between cigarette use and epilepsy., Systematic Review Registration: CRD42022342510., (© 2024. The Author(s).)

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting the voluntary motor nervous system. Several observational studies have provided conflicting results regarding the association between smoking and ALS. Therefore, our objective was to investigate this association through a systematic review, meta-analysis, and dose-response analysis., Methods: On 16 January 2023, we initially extracted records from medical databases, which included Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included case-control and cohort studies as eligible studies. Subgroup analyses were performed based on sex, study design, and current smoking. Restricted cubic-spline analysis was utilized to assess the dose-response relationship between smoking (pack-years) and ALS., Results: Twenty-eight case-control and four cohort studies met the inclusion criteria. The unadjusted OR for the overall association between smoking and ALS was 1.14 (95% CI: 1.06-1.22, I 2 =44%, p<0.001), and the adjusted OR (AOR) was 1.12 (95% CI: 1.03-1.21, I 2 =49%, p=0.009). Subgroup analysis revealed a more pronounced association among current smokers, with an AOR of 1.28 (95% CI: 1.10-1.49, I 2 =66%, p<0.001) and AOR of 1.28 (95% CI: 1.10-1.48, I 2 =58%, p=0.001). In the dose-response analysis, the non-linear model revealed an inverted U-shaped curve., Conclusions: Our study provides evidence of a positive relationship between smoking and the risk of ALS. To mitigate the risk of developing ALS, discontinuing smoking, which is a modifiable risk factor, may be crucial. TRIAL REGISTRATION: The study was registered in PROSPERO. IDENTIFIER: CRD42023388822., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Kim K. et al.)

White blood cells (WBCs) act as mediators of inflammatory responses and are commonly measured in hospitals. Although several studies have reported a relation between WBC count and mortality, no systematic review or meta-analysis has been conducted. This study aimed to identify an association between WBC count and mortality. We conducted a systematic search on Embase using keywords such as "white blood cell" and "mortality." We analyzed the hazard ratios (HRs) for WBC count of 1.0 × 10 9 cells/L regarding 2 criteria: the cause of mortality and the follow-up period. A total of 13 of 222 articles comprising a total of 62,904 participants were included in this study, meeting the criteria set. A positive association was observed between WBC count and mortality, as indicated by an HR of 1.10 (95% confidence interval [CI] 1.08 to 1.13). In additionally, WBC count emerged as a significant predictor of mortality in both groups, with an HR of 1.10 (95% CI 1.07 to 1.12) for patients with cardiovascular disease and an HR of 1.12 (95% CI 1.07 to 1.17) for the general population or patients with COVID-19. Furthermore, a higher WBC count demonstrated a significant association with long-term all-cause mortality (HR 1.09, 95% CI 1.07 to 1.12) and long-term cardiovascular mortality (HR 1.05, 95% CI 1.02 to 1.07). Similarly, a significant association was found between higher WBC count and short-term all-cause mortality (HR 1.12, 95% CI 1.09 to 1.16) and cardiovascular mortality (HR 1.12, 95% CI 1.07 to 1.17). Further research is necessary to explore the relation between WBC count and disease progression or death and to establish causality between elevated WBC count and disease progression., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Despite advances in the maintenance of arteriovenous fistulas (AVFs), the patency rates remain suboptimal. Most AVFs fail due to outflow vein stenosis; however, the underlying mechanism of AVF stenosis remains unclear. The present study aimed to identify key factors associated with AVF outflow stenosis., Methods: We obtained gene expression profiling data for the outflow vein of AVF from three Gene Expression Omnibus database datasets (GSE39488, GSE97377, and GSE116268) and analyzed the common differentially expressed genes (DEGs). We evaluated a common DEG in an aortocaval mouse model and the stenotic outflow veins of AVFs collected from patients. Furthermore, we isolated vascular smooth muscle cells (VSMCs) from the inferior vena cava (IVC) of wild-type (WT) and osteopontin (Opn)-knockout (KO) mice and assessed the proliferation of VSMCs following stimulation with platelet-derived growth factors (PDGFs)., Results: OPN was the only common upregulated DEG among all datasets. OPN was expressed in the medial layer of the outflow vein of AVF in aortocaval mouse models and co-stained with the VSMC marker (α-smooth muscle actin). OPN expression was markedly increased in the VSMCs of stenotic outflow veins of AVF collected from patients undergoing hemodialysis compared to presurgical veins acquired during AVF formation surgery. PDGF-induced VSMC proliferation was significantly increased in the VSMCs isolated from the IVC of WT mice but not in those isolated from the IVC of Opn-KO mice., Conclusions: OPN may be a key gene involved in VSMC proliferation in the AVF outflow veins and a therapeutic target to improve the AVF patency rate., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Chimeric lysins composed of various combinations of cell wall-lysing (enzymatic) and cell-wall-binding (CWB) domains of endolysins, autolysins, and bacteriocins have been developed as alternatives to or adjuvants of conventional antibiotics. The screening of multiple chimeric lysin candidates for activity via E. coli expression is not cost effective, and we previously reported on a simple cell-free expression system as an alternative. In this study, we sufficiently improved upon this cell-free expression system for use in screening activity via a turbidity reduction test, which is more appropriate than a colony reduction test when applied in multiple screening. Using the improved protocol, we screened and compared the antibacterial activity of chimeric lysin candidates and verified the relatively strong activity associated with the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain of secretory antigen SsaA-like protein (ALS2). ALS2 expressed in E. coli showed two major bands, and the smaller one (subprotein) was shown to be expressed by an innate downstream promoter and start codon (ATG). The introduction of synonymous mutations in the promoter resulted in clearly reduced expression of the subprotein, whereas missense mutations in the start codon abolished antibacterial activity as well as subprotein production. Interestingly, most of the S. aureus strains responsible for bovine mastitis were susceptible to ALS2, but those from human and chicken were less susceptible. Thus, the simple and rapid screening method can be applied to select functional chimeric lysins and define mutations affecting antibacterial activity, and ALS2 may be useful in itself and as a lead molecule to control bovine mastitis.

Vascular smooth muscle cell (VSMC) proliferation is a hallmark of neointimal hyperplasia (NIH) in atherosclerosis and restenosis post-balloon angioplasty and stent insertion. Although numerous cytotoxic and cytostatic therapeutics have been developed to reduce NIH, it is improbable that a multifactorial disease can be successfully treated by focusing on a preconceived hypothesis. We, therefore, aimed to identify key molecules involved in NIH via a hypothesis-free approach. We analyzed four datasets (GSE28829, GSE43292, GSE100927, and GSE120521), evaluated differentially expressed genes (DEGs) in wire-injured femoral arteries of mice, and determined their association with VSMC proliferation in vitro . Moreover, we performed RNA sequencing on platelet-derived growth factor (PDGF)-stimulated human VSMCs (hVSMCs) post-phosphoenolpyruvate carboxykinase 2 ( PCK2 ) knockdown and investigated pathways associated with PCK2. Finally, we assessed NIH formation in Pck2 knockout (KO) mice by wire injury and identified PCK2 expression in human femoral artery atheroma. Among six DEGs, only PCK2 and RGS1 showed identical expression patterns between wire-injured femoral arteries of mice and gene expression datasets. PDGF-induced VSMC proliferation was attenuated when hVSMCs were transfected with PCK2 siRNA. RNA sequencing of PCK2 siRNA-treated hVSMCs revealed the involvement of the Akt-FoxO-PCK2 pathway in VSMC proliferation via Akt2, Akt3, FoxO1, and FoxO3. Additionally, NIH was attenuated in the wire-injured femoral artery of Pck2 -KO mice and PCK2 was expressed in human femoral atheroma. PCK2 regulates VSMC proliferation in response to vascular injury via the Akt-FoxO-PCK2 pathway. Targeting PCK2, a downstream signaling mediator of VSMC proliferation, may be a novel therapeutic approach to modulate VSMC proliferation in atherosclerosis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The surgical workforce, like the rest of the population, is ageing. This has raised concerns about the association between the age of the surgeon and their surgical outcomes. We performed a systematic review and meta-analysis of cohort studies on postoperative mortality and major morbidity according to the surgeons' age. The search was performed on February 2021 using the Embase, Medline and CENTRAL databases. Postoperative mortality and major morbidity were evaluated as clinical outcomes. We categorized the surgeons' age into young-, middle-, and old-aged surgeons. We compared the differences in clinical outcomes for younger and older surgeons compared to middle-aged surgeons. Subgroup analyses were performed for major and minor surgery. Ten retrospective cohort studies on 29 various surgeries with 1,666,108 patients were considered. The mortality in patients undergoing surgery by old-aged surgeons was 1.14 (1.02-1.28, p = 0.02) (I 2  = 80%) compared to those by middle-aged surgeon. No significant differences were observed according to the surgeon's age in the major morbidity and subgroup analyses. This meta-analysis indicated that surgeries performed by old-aged surgeons had a higher risk of postoperative mortality than those by middle-aged surgeons. Thus, it necessitates the introduction of a multidisciplinary approach to evaluate the performance of senior surgeons., (© 2022. The Author(s).)

Background: Epilepsy is one of the most common neurological disorders, affecting approximately 50 million people worldwide. Although a positive association between alcohol consumption and epilepsy has been demonstrated in previous meta-analyses of case-control studies, the results of several recently published large cohort studies are contradictory. Therefore, we conducted an updated meta-analysis that included more recent data to clarify the association between alcohol consumption and epilepsy., Methods: The search was performed on 25 January 2021 using the Embase and MEDLINE databases. Cohort or case-control studies were eligible for inclusion in this study. We used restricted cubic spline analysis to perform a dose-response meta-analysis., Results: A total of eight studies, including three cohort and five case-control studies, were included in our meta-analysis. The pooled risk of epilepsy was 1.70 (1.16-2.49) in alcohol users compared to non-drinkers. Subgroup analysis of 50 g units showed that the epilepsy risk increased as alcohol intake increased. The pooled risk of cohort studies was 1.00 (0.65-1.54), and the pooled risk of case-control studies was 2.61 (1.29-5.29). According to the dose-response analysis, the regression coefficient was 1.009 (1.004-1.014), indicating a significant positive dose-response relationship., Conclusion: Unlike the case-control studies, the cohort studies did not reveal a significant association between alcohol consumption and epilepsy. Further large cohort studies for the general population are required to assert a definite causal relationship between alcohol consumption and epilepsy and to identify a potential threshold., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Non-toxic InP-based nanocrystals have been developed for promising candidates for commercial optoelectronic applications and they still require further improvement on photophysical properties, compared to Cd-based quantum dots (QDs), for better device efficiency and long-term stability. It is, therefore, essential to understand the precise mechanism of carrier trapping even in the state-of-the-art InP-based QD with near-unity luminescence. Here, it is shown that using time-resolved spectroscopic measurements of systematically size-controlled InP/ZnSe/ZnS core/shell/shell QDs with the quantum yield close to one, carrier trapping decreases with increasing the energy difference between band-edge and trap states, indicating that the process follows the energy gap law, well known in molecular photochemistry for nonradiative internal conversion between two electronic states. Similar to the molecular view of the energy gap law, it is found that the energy gap between the band-edge and trap states is closely associated with ZnSe phonons that assist carrier trapping into defects in highly luminescent InP/ZnSe/ZnS QDs. These findings represent a striking departure from the generally accepted view of carrier trapping mechanism in QDs in the Marcus normal region, providing a step forward understanding how excitons in nanocrystals interact with traps, and offering valuable guidance for making highly efficient and stable InP-based QDs., (© 2021 Wiley-VCH GmbH.)

Purpose: Intensive care unit (ICU) bed availability is key to critical patient care. In many countries, older patients generally account for a significant proportion of hospitalizations and ICU admissions. Therefore, considering the rapidly increasing aging population in South Korea, it is important to establish whether the demand for critical care is currently met by available ICU beds., Materials and Methods: We evaluated a 9-year trend in ICU bed supply and ICU length of stay in South Korea between 2011 and 2019 in a population-based cross-sectional analysis, using data from the Korean Health Insurance Review & Assessment Service and Statistics database. We described the changes in ICU bed rates in adult (≥20 years) and older adult (≥65 years) populations. ICU length of stay was categorized similarly and was used to predict future ICU bed demands., Results: The ICU bed rate per 100000 adults increased from 18.5 in 2011 to 19.5 in 2019. In contrast, the ICU bed rate per 100000 older adults decreased from 127.6 in 2011 to 104.0 in 2019. ICU length of stay increased by 43.8% for adults and 55.6% for older adults. In 2019, the regional differences in the ICU bed rate nearly doubled, and the ICU length of stay increased six-fold. The ICU bed occupancy rate in South Korea is expected to rise to 102.7% in 2030., Conclusion: The discrepancy between the demand and supply of ICU beds in South Korea requires urgent action to anticipate future ICU demands., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2021.)

Humans may serve as a reservoir host of Staphylococcus aureus, resulting in transmission to animals. Previously, we used RNA polymerase beta subunit gene (rpoB)-based genotyping and classified S. aureus strains into rpoB sequence types (RSTs). According to our previous work, the predominant genotypes of S. aureus in humans and cows differ in Korea, but some predominant genotypes (RST4-1 and RST2-1) in humans have been isolated from bovine mastitis. Therefore, it needs to be determined whether some strains of the predominant human genotypes have adapted to or caused occasional infections in cows. We determined the whole genome sequences of 2 bovine mastitis-origin strains, PMB179 (RST4-1) and PMB196 (RST2-1), and performed comparative genomics with the corresponding RST4-1 and RST2-1 S. aureus strains in the NCBI database. We identified 257 and 180 pseudogenes among 131 RST4-1 and 54 RST2-1 strains, respectively, for the comparison of pseudogene profiles. RST4-1 strains shared more common pseudogenes than RST2-1 strains, and some epidemiologically related strains shared common pseudogenes. However, most of the pseudogenes were strain-specific, and diverse pseudogene profiles were apparent in both the RST4-1 and RST2-1 strains. Furthermore, analysis of the mobile genetic elements, virulence genes, and antibiotic resistance genes revealed no molecular markers to differentiate PMB179 and PMB196 from human strains. Interestingly, the collective comparison of RST4-1 or RST2-1 strains revealed cumulative acquisition steps of genomic islands and antibiotic resistance genes. In conclusion, our data support PMB179 and PMB196 causing occasional infections that result in bovine mastitis., (Copyright © 2021. Published by Elsevier Ltd.)

A recent meta-analysis addressed increased risk of death following revascularization with paclitaxel-coated devices in femopopliteal artery. We evaluated differences in all-cause mortality and amputation free survival between peripheral arterial disease (PAD) patients who were treated with paclitaxel-coated devices and non-paclitaxel-coated devices. This was retrospective population-based cohort study from the National Health Insurance Service claims in South Korea from 2015 to 2019. Multivariate Cox regression analyses after propensity score matching were applied to identify all-cause mortality and amputation-free survival. After propensity score matching, there were 6090 patients per group. The median follow-up days was 580 days (interquartile range [IQR] 240-991 days) and 433 days (IQR 175-757 days) for the non-paclitaxel-coated device group and paclitaxel-coated device group, respectively. Multivariate analysis adjusted for age, sex, diabetes, hypertension, warfarin, and new oral anticoagulants showed that the mortality rate associated with paclitaxel-coated devices was not significantly higher than non-paclitaxel-coated devices (hazard ratio [HR] 0.992; 95% CI 0.91-1.08). The rate of amputation events was higher in patients with paclitaxel-coated devices than those with non-paclitaxel-coated devices (HR 1.614; 95% CI 1.46-1.78). In this analysis, the mortality rate in patients with PAD was not associated with the use of paclitaxel-coated devices, despite a higher amputation rate., (© 2021. The Author(s).)

Background: Diabetic peripheral neuropathy (DPN), the most common microvascular complication of type-2 diabetes mellitus (T2DM), results in nontraumatic lower-limb amputations. When DPN is not detected early, disease progression is irreversible. Thus, biomarkers for diagnosing DPN are needed., Methods: We analyzed three data sets of T2DM DPN: two for mouse models (GSE70852 and GSE34889) and one for a human model (GSE24290). We found common differentially expressed genes (DEGs) in the two mouse data sets and validated them in the human data set. To identify the phenotypic function of the DEGs, we overexpressed them in zebrafish embryos. Clinical information and serum samples of T2DM patients with and without DPN were obtained from the Korea Biobank Network. To assess the plausibility of DEGs as biomarkers of DPN, we performed an enzyme-linked immunosorbent assay., Results: Among the DEGs, only NPY and SLPI were validated in the human data set. As npy is conserved in zebrafish, its mRNA was injected into zebrafish embryos, and it was observed that the branches of the central nervous system became thicker and the number of dendritic branches increased. Baseline characteristics between T2DM patients with and without DPN did not differ, except for the sex ratio. The mean serum NPY level was higher in T2DM patients with DPN than in those without DPN ( p  = 0.0328), whereas serum SLPI levels did not differ ( p  = 0.9651)., Conclusion: In the pathogenesis of DPN, NPY may play a protective role in the peripheral nervous system and may be useful as a biomarker for detecting T2DM DPN., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2021.)

Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences. Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT). Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach. Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers. Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology. Panel: Research in context., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by Elsevier Ltd.)

Background: Ultrasound-guided regional anesthesia has gained popularity over the last decade. This study aimed to assess whether YouTube videos sufficiently serve as an adjunctive tool for learning how to perform an ultrasound-guided brachial plexus block (BPB)., Methods: All YouTube videos were classified, based on their sources, as either academic, manufacturer, educational, or individual videos. The metrics, accuracy, utility, reliability (using the Journal of American Medical Association Score benchmark criteria (JAMAS)), and educational quality (using the Global Quality Score (GQS) and Brachial Plexus Block Specific Quality Score (BSQS)) were validated., Results: Here, 175 videos were included. Academic (1.19 ± 0.62, mean ± standard deviation), manufacturer (1.17 ± 0.71), and educational videos (1.15 ± 0.76) had better JAMAS accuracy and reliability than individual videos (0.26 ± 0.67) ( p < 0.001). Manufacturer (11.22 ± 1.63) and educational videos (10.33 ± 3.34) had a higher BSQS than individual videos (7.32 ± 4.20) ( p < 0.001). All sources weakly addressed the equipment preparation and post-procedure questions after BSQS analysis., Conclusions: The reliability and quality of ultrasound-guided BPB videos differ depending on their source. As YouTube is a useful educational platform for learners and teachers, global societies of regional anesthesiologists should set a standard for videos.

Opioid prescribing data can guide regulation policy by informing trends and types of opioids prescribed and geographic variations. In South Korea, the nationwide data on prescribing opioids remain unclear. We aimed to evaluate an 11-year trend of opioid prescription in South Korea, both nationally and by administrative districts. A population-based cross-sectional analysis of opioid prescriptions dispensed nationwide in outpatient departments between January 1, 2009, and December 31, 2019, was conducted for this study. Data were obtained from the Health Insurance Review & Assessment Service. The types of opioids prescribed were categorized into total, strong, and extended-release and long-acting formulation. Trends in the prescription rate per 1000 persons were examined over time nationally and across administrative districts. There are significant increasing trends for total, strong, and extended-release and long-acting opioid prescriptions (rate per 1000 persons in 2009 and 2019: total opioids, 347.5 and 531.3; strong opioids, 0.6 and 15.2; extended-release and long-acting opioids, 6.8 and 82.0). The pattern of dispensing opioids increased from 2009 to 2013 and slowed down from 2013 to 2019. The rate of opioid prescriptions issued between administrative districts nearly doubled for all types of opioids. Prescription opioid dispensing increased substantially over the study period. The increase in the prescription of total opioids was largely attributed to an increase in the prescription of weak opioids. However, the increase in prescriptions of extended-release and long-acting opioids could be a future concern. These data may inform government organizations to create regulations and interventions for prescribing opioids., Competing Interests: The authors have declared that no competing interests exist.

The bevel structure of organic multilayers produced by finely controlled Ar gas cluster ion beam sputtering preserves both the molecular distribution and chemical states. Nevertheless, there is still an important question of whether this method can be applicable to organic multilayer structures composed of complex or ambiguous interfaces used in real organic optoelectronic devices. Herein, various bevel structures are fabricated from different types of organic semiconductors using a solution-based deposition technique: complicatedly intermixed electron-donor and electron-acceptor bulk heterojunction structure, thin film structure with an internal donor-acceptor concentration gradient, and multi-layered structure with more than three layers. For these organic material combinations listed above, the bevel structure is fabricated with finely tuned Ar gas cluster ion beam sputtering. The location-dependent X-ray photoelectron spectroscopy (XPS) results obtained for each bevel structure exactly correspond to the XPS depth profiles. This result demonstrates that the bevel structure analysis is a powerful method to distinguish subtle differences in chemical component distributions and chemical states of organic semiconductors even with complex or ambiguous interfaces. Ultimately, due to its reliability as verified by this study, the proposed bevel structure analysis is expected to greatly expand other analytical techniques with a limited spatial or depth resolution., (© 2021 Wiley-VCH GmbH.)

The multidecadal expansion of northern Gulf of Mexico continental shelf hypoxia is a striking example of the adverse effects of anthropogenic nutrient enrichment on coastal oceans. Increased nutrient inputs and widespread shelf hypoxia have resulted in numerous dissolved oxygen (DO) water quality problems in nearshore coastal waters of Louisiana. A large hydrographic dataset compiled from research programs spanning 30 years and the three-dimensional hydrodynamic-biogeochemical model CGEM (Coastal Generalized Ecosystem Model) were integrated to explore the interconnections of low DO waters across the continental shelf to nearshore coastal waters of Louisiana. Cross-shelf vertical profiles showed contiguous low DO bottom waters extending from the shelf to coastal waters nearly every year in the 30+ year time series, which were concurrent with strong cross-shelf pycnoclines. A threshold Brunt-Väisälä frequency of 40 cycles h -1 was critical to maintaining the cross-shelf subpycnocline layers and facilitating the formation of a contiguous low DO water mass. Field observations and model simulations identified periods of wind-driven bottom water upwelling lasting between several days to several weeks, resulting in both physical advection of oxygen-depleted offshore waters to the nearshore and enhanced nearshore stratification. Both the upwelling of low DO bottom waters and in situ respiration were of sufficient temporal and spatial extent to drive DO below Louisiana's DO water quality criteria. Basin-wide nutrient management strategies aimed at reducing nutrient inputs and shelf hypoxia remain essential to improving the nearshore coastal water quality across the northern Gulf of Mexico.

Facile strategies in flexible transparent conductive electrode materials that can sustain their electrical conductivities under 1 mm-scale radius of curvature are required for wider applications such as foldable devices. We propose a rational design as well as a fabrication process for a silver nanowire-based transparent conductive electrode with low sheet resistance and high transmittance even after prolonged cyclic bending. The electrode is fabricated on a poly(ethylene terephthalate) film through the hybridization of silver nanowires with silver nanoparticles-anchored RuO 2 nanosheets. This hybridization significantly improves the performance of the silver nanowire network under severe bending strain and creates an electrically percolative structure between silver nanowires and RuO 2 nanosheets in the presence of anchored silver nanoparticles on the surface of RuO 2 nanosheets. The resistance change of this hybrid transparent conductive electrode is 8.8% after 200,000 bending cycles at a curvature radius of 1 mm, making it feasible for use in foldable devices.

The live attenuated vaccine strain, SG9R, has been used against fowl typhoid worldwide, but it can revert to the pathogenic smooth strain owing to single nucleotide changes such as nonsense mutations in the rfaJ gene. As SG9R possesses an intact Salmonella plasmid with virulence genes, it exhibits dormant pathogenicity and can cause fowl typhoid in young chicks and stressed or immunocompromised brown egg-laying hens. To tackle these issues, we knocked out the rfaJ gene of SG9R (named Safe-9R) to eliminate the reversion risk and generated detoxified strains of Safe-9R by knocking out lpxL , lpxM , pagP , and phoP/phoQ genes to attenuate the virulence. Among the knockout strains, live Δ lpxL - (Dtx-9RL) and Δ lpxM -9R (Dtx-9RM) strains induced remarkably less expression of inflammatory cytokines in chicken macrophage cells, and oil emulsion (OE) Dtx-9RL did not cause body weight loss in chicks. Live Dtx-9RM exhibited efficacy against field strain challenge in one week without any bacterial re-isolation, while the un-detoxified strains showed the development of severe liver lesions and re-isolation of challenged strains. Thus, SG9R was optimally detoxified by knockout of lpxL and lpxM , and Dtx-9RL and Dtx-9RM might be applicable as OE and live vaccines, respectively, to prevent fowl typhoid irrespective of the age of chickens.

Abdominal aortic aneurysm (AAA), when ruptured, results in high mortality. The identification of molecular pathways involved in AAA progression is required to improve AAA prognosis. The aim of the present study was to assess the key genes for the progression of AAA and their functional role. Genomic and clinical data of three independent cohorts were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) (GSE57691, GSE7084, and GSE98278). To develop AAA diagnosis and progression-related differentially expressed genes (DEGs), we used a significance analysis of microarray (SAM). Spearman correlation test and gene set analysis were performed to identify potential enriched pathways for DEGs. Only the Frizzled-related protein (FRZB) gene and chromosome 1 open reading frame 24 (C1orf24) exhibited significant down-regulation in all analyses. With FRZB, the pathways were associated with RHO GTPase and elastin fiber formation. With C1orf24, the pathways were elastic fiber formation, extracellular matrix organization, and cell-cell communication. Since only FRZB was evolutionally conserved in the vertebrates, function of FRZB was validated using zebrafish embryos. Knockdown of frzb remarkably reduced vascular integrity in zebrafish embryos. We believe that FRZB is a key gene involved in AAA initiation and progression affecting vascular integrity., (© 2021 The Author(s).)

Objective: Colorectal cancer is presently the third most commonly diagnosed cancer in the United States. In this study, we identified molecular differences between hepatic and non-hepatic metastases in colorectal cancer and evaluated their prognostic significance., Materials and Methods: We downloaded primary data from the NCBI Gene Expression Omnibus (GSE6988, GSE62321, GSE50760, and GSE28722). To identify the molecular differences, we used the Significance Analysis of Microarray method. We selected nine prognostic genes (SYTL2, PTPLAD1, CDS1, RNF138, PIGR, WDR78, MYO7B, TSPAN3, and ATP5F1) with hepatic metastasis prediction score in colorectal cancer (hereafter referred to as LASSO Score). We confirmed the prognostic significance of the LASSO Score by using Kaplan-Meier survival analysis, multivariate analysis, the time-dependent area under the curve (AUC) of Uno's C-index, and the AUC of the receiver operating characteristic curve at 1-5 years., Results: Survival analysis revealed that a high LASSO Score is associated with a poor prognosis in colorectal cancer patients with hepatic metastases (p = 0). Analysis of C-indices and AUC values from the receiver operating characteristic curve further supported this prediction by the LASSO Score. Multivariate analysis confirmed the prognostic significance of the LASSO Score (p = 1.13e-06)., Conclusions: This study reveals the biological mechanisms underlying hepatic metastases in colorectal cancer and will help in developing targeted therapies for colorectal cancer.

Purpose: Owing to its worldwide spread, the coronavirus disease (COVID-19) epidemic was declared a pandemic by the World Health Organization on March 11, 2020. Angiotensin-converting enzyme 2 (ACE2) is the outer surface protein of the cell membrane that is abundantly distributed in the heart, lungs, and kidneys and plays an important role in molecular docking of the severe acute respiratory syndrome coronavirus 2. In this study, we aimed to analyze the difference in the survival rate according to ACE2 expressions in pan-cancer., Materials and Methods: We downloaded clinical and genomic data from The Cancer Genome Atlas. We used Kaplan-Meier with a log-rank test, and the Cox proportional hazards regression to analyze prognostic significance., Results: In the Kaplan-Meier curve, clear cell renal cell carcinoma (ccRCC), uveal melanoma, and prostate adenocarcinoma showed statistical significance. In the Cox regression, thyroid carcinoma and glioblastoma multiforme and ccRCC showed significant results. Only ccRCC had statistical significance, and high ACE2 expression is related to good prognosis. It is known that the ACE inhibitor, a primary antihypertensive agent, increases ACE2 expression., Conclusion: Based on these results, we believe that the ACE inhibitor will be important to increase the lifespan of ccRCC patients. This study is the first research to offer a recommendation on the use of anti-hypertensive drugs to ccRCC patients., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Kihun Kim et al.)

Fowl typhoid is caused by Salmonella enterica serovar Gallinarum biovar Gallinarum (SG), and live attenuated, rough vaccine strains have been used. Both humoral and cellular immune responses are involved in protection, but the humoral responses to different forms of SG antigens are unclear. In this study, we compared humoral responses to a killed oil-emulsion (OE) smooth vaccine (SG002) and its rough mutant vaccine (SR2-N6) strains using proteomics techniques. We identified two immunogenic outer membrane proteins (OmpA and OmpX), and the selected linear epitopes were successfully applied in peptide-ELISA. Our peptide- and total OMP-ELISAs were used to compare the temporal humoral responses to various SG antigens: OE SG002 and SR2-N6; live, killed [PBS-suspension (PS) and OE)] and mixed (live and PS) formulations of another rough vaccine strain (SG 9R); and orally challenge with a field strain. Serum antibodies to the linear epitopes of OmpA and OmpX lasted only for the first 2 weeks, but serum antibodies against OMPs increased over time. The rough strain (SR2-N6) and mixed SG 9R induced higher serum antibody titers than the smooth strain (SG002) and single SG 9R (OE, live and PS SG 9R), respectively. Infection with the field strain delayed the serum antibody response by ~2 weeks. Mucosal immunity was not induced by any formulation, except for infection with the field strain after SG 9R vaccination. Thus, our results may be useful to understand humoral immunity against various SG antigens and to improve vaccine programs and serological diagnosis in the field., (Copyright © 2020 Kim, Ha, Ko, Choi and Kwon.)

Background/aim: Since pathways involving LRRC17 are related to the survival of patients with various cancers, we analyzed LRRC17 as a prognostic gene in serous ovarian cancer., Materials and Methods: Data were collected from Gene Expression Omnibus (GSE9891, GSE13876, and GSE26712) and The Cancer Genome Atlas (TCGA). We performed survival analyses using C statistics, area under the curve, survival plot with optimal cutoff level, and cox proportional regression. Zebrafish embryos were used as an in vivo model., Results: The prognosis of patients with high LRRC17 expression was poorer than that of patients with low LRRC17 expression. Multivariate regression analysis showed that LRRC17 expression, age, and stage were independently related with survival. Knockdown of lrrc17 reduced survival rate and delayed development in zebrafish embryos. We also found that lrrc17 is important for cell viability by protecting from p53-dependent apoptosis., Conclusion: LRRC17 could be a prognostic gene in ovarian cancer as it regulates cancer cell viability through the p53 pathway., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: High cathepsin D has been associated with poor prognosis in breast cancer; however, the results of many studies are controversial. Here, we assessed the association between high cathepsin D levels and worse breast cancer prognosis by conducting a meta-analysis., Methods: A comprehensive search strategy was used to search relevant literature in PUBMED and EMBASE by September 2018. The meta-analysis was performed in Review Manager 5.3 using hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: A total of 15,355 breast cancer patients from 26 eligible studies were included in this meta-analysis. Significant associations between elevated high cathepsin D and poor overall survival (OS) (HR = 1.61, 95% CI: 1.35-1.92, p  < 0.0001) and disease-free survival (DFS) (HR = 1.52, 95% CI: 1.31-2.18, p  < 0.001) were observed. In the subgroup analysis for DFS, high cathepsin D was significantly associated with poor prognosis in node-positive patients (HR = 1.38, 95% CI: 1.25-1.71, p  < 0.00001), node-negative patients (HR = 1.78, 95% CI: 1.39-2.27, p  < 0.0001), early stage patients (HR = 1.73, 95% CI: 1.34-2.23, p  < 0.0001), and treated with chemotherapy patients (HR = 1.60, 95% CI: 1.21-2.12, p  < 0.001). Interestingly, patients treated with tamoxifen had a low risk of relapse when their cathepsin D levels were high (HR = 0.71, 95% CI: 0.52-0.98, p  = 0.04) and a high risk of relapse when their cathepsin D levels were low (HR = 1.50, 95% CI: 1.22-1.85, p  = 0.0001)., Conclusions: Our meta-analysis suggests that high expression levels of cathepsin D are associated with a poor prognosis in breast cancer. Based on our subgroup analysis, we believe that cathepsin D can act as a marker for poor breast cancer prognosis and also as a therapeutic target for breast cancer., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Adolescent idiopathic scoliosis is the most common spinal deformity during puberty, especially in females. It is characterized by aberrant skeletal growth and generalized reduced bone density, which is associated with impaired bone mineral metabolism. Despite recent progress in multidisciplinary research to support various hypotheses, the pathogenesis of Adolescent idiopathic scoliosis is still not clearly understood. One of the hypothesis is to study the role of mesenchymal stem cells due to its involvement in the above-mentioned bone metabolic abnormalities. In this review, we will summarize reported literatures on the role of mesenchymal stem cells, particularly in the pathogenesis of Adolescent idiopathic scoliosis. In addition, we will describe the research on mesenchymal stem cells of Adolescent idiopathic scoliosis performed using bioinformatics tools., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Bacteroides thetaiotaomicron (B. thetaiotaomicron), which resides in the human intestinal tract, has a number of carbohydrate enzymes, including glycoside hydrolase (GH) family 97. Only a few GH 97 enzymes have been characterized to date. In this study, a novel α-galactosidase (Bt&#95;3294) was cloned from B. thetaiotaomicron, expressed in Escherichia coli, and purified using affinity chromatography. This novel enzyme showed optimal activity at 60 °C and pH 7.0. Enzyme activity was reduced by 94.4% and 95.7% in the presence of 5 mM Ca 2+ and Fe 2+ , respectively. It is interesting that Bt&#95;3294 specifically hydrolyzed shorter α-galactosyl oligosaccharides, such as melibiose and raffinose. The D-values of Bt&#95;3294 at 40 °C and 50 °C were about 107 and 6 min, respectively. After immobilization of Bt&#95;3294, the D-values at 40 °C and 50 °C were about 37.6 and 29.7 times higher than those of the free enzyme, respectively. As a practical application, the immobilized Bt&#95;3294 was used to hydrolyze raffinose family oligosaccharides (RFOs) in soy milk, decreasing the RFOs by 98.9%., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Temporal variation in seawater temperature plays a crucial role in coral reef ecology. Nanwan Bay, Southern Taiwan is home to well-developed coral reefs, which frequently experience cold-water intrusions caused by internal wave-induced upwelling, that manifest in distinct daily temperature minima. These temperature minima and their associated sources were studied by recording in situ bottom temperatures and sea levels observed at depths of 5 and 30 m from May 2007 to September 2008. These data were then compared to the East Asian Seas Nowcast/Forecast System, and it was found that daily temperature minima presented large variations with magnitudes of 2-3 °C over periods from days to months. It was further demonstrated that the cold-water intrusions may have originated from depths of ~100 m and were strongly affected by westward propagating mesoscale eddies from the Pacific basin. An impinging warm anticyclonic eddy in July 2007 may have combined with the El Niño, resulting in temperatures surpassing 29 °C and degree heating days >4.0 °C-days at both depths, which were coincidental with a mass coral bleaching event. This eddy's impact was additionally evident in high correlations between daily temperature minima and residual sea levels, suggesting that mesoscale eddies alter stratification, substantially influence temperature variation, and play important roles in understanding ecological processes on coral reefs.

The hypoxic zone on the Louisiana Continental Shelf (LCS) forms each summer due to nutrient enhanced primary production and seasonal stratification associated with freshwater discharges from the Mississippi/Atchafalaya River Basin (MARB). Recent field studies have identified highly productive shallow nearshore waters as an important component of shelf-wide carbon production contributing to hypoxia formation. In this study we present results from a three-dimensional hydrodynamic-biogeochemical model named CGEM (Coastal Generalized Ecosystem Model) applied to quantify the spatial and temporal patterns of hypoxia, carbon production, respiration, and transport between nearshore and middle shelf regions where hypoxia is most prevalent. We first demonstrate that our simulations successfully reproduced spatial and temporal patterns of carbon production, respiration, and bottom-water oxygen gradients compared to field observations. We then used interannual simulations to identify transport of particulate organic carbon (POC) from nearshore areas where riverine organic matter and phytoplankton carbon production are greatest. The spatial disconnect between carbon production and respiration in our simulations was driven by westward and offshore POC flux, a pattern that supported heterotrophic respiration on the middle shelf where hypoxia is frequently observed. These results validate the importance of offshore carbon flux to hypoxia formation, particularly on the west shelf where hypoxic conditions are more variable.

Milk fat globule-EGF factor 8 (MFG-E8) is an anti-inflammatory glycoprotein that mediates a wide spectrum of pathophysiological processes. MFG-E8 has been studied as a key regulator of cancer cell invasion, migration, and proliferation in different tissues and organs. However, potential roles of MFG-E8 in the growth and progression of liver cancer have not been investigated to date. Here, we analyzed 33 human hepatocellular carcinoma (HCC) samples and found that levels of MFG-E8 expression were significantly higher in HCC cells than in normal liver tissues. In addition, our in vitro gain-of-function study in three different HCC cell lines revealed that overexpression of MFG-E8 promoted the proliferation and migration of HCC cells, as determined by RT-qPCR, MTT assays, and wound healing analyses. Conversely, an MFG-E8 loss-of function study showed that proliferation capacity was significantly reduced by MFG-E8 knockdown in HCC cells. Additionally, MFG-E8 activity-neutralizing antibodies profoundly inhibited both migration and proliferation of HCC cells, attenuating their tumorigenic properties. These reductions in migration and proliferation were rescued by treatment of HCC cells with recombinant MFG-E8 protein. Furthermore, an in vivo HCC xenograft study showed that the number of proliferating HCC cells and tumor volume/weight were all significantly increased by MFG-E8 overexpression, compared to control mice. These results clearly show that MFG-E8 plays an important role in HCC progression and may provide a basis for future mechanistic studies and new strategies for the treatment of liver cancer., Competing Interests: The authors declare no conflict of interest.

The widely-studied ferromagnetic van-der-Waals (vdW) metal Fe 3 GeTe 2 has great promise for studies of quantum criticality in the 2D limit, but is limited by a relatively high Curie temperature in excess of 200 K. To help render the quantum critical point achievable in such a system within the reach of practically possible tuning methods, we have grown single crystals of a variant of (Fe,Co) 3 GeTe 2 with useful physical properties for both this purpose and the wider study of low-dimensional magnetism and spin transport. (Fe,Co) 3 GeTe 2 is found through x-ray diffraction and electron microscopy to have an equivalent crystal structure to Fe 3 GeTe 2 , with a random distribution of the cobalt dopant sites. It exhibits a sharp ferromagnetic transition at a value below 40 K, a stronger anisotropy and a coercive field ten times larger than that of Fe 3 GeTe 2 . The transport properties and specific heat show the electronic properties and strong correlations of Fe 3 GeTe 2 to be near-unchanged in this doped material. We demonstrate that (Fe,Co) 3 GeTe 2 can be cleanly exfoliated down to monolayer thickness. This unprecedented hard metallic vdW ferromagnet is a valuable new addition to the limited range of materials available for the study of 2D magnetism.

This study investigated the effect of octylphenol (OP) and nonylphenol (NP) on decidualization of endometrial stromal cells. Telomerase-immortalized human endometrial stromal cells were cultured for 12 days and decidualization was induced in vitro. The cells were exposed to OP (5 or 10 μM) or NP (5 μM) during in vitro decidualization. The expression levels of decidualization markers were analyzed using qRT-PCR. The amount of prolactin (PRL) and insulin-like growth factor binding protein 1 (IGFBP1) was measured in medium using ELISA. The expression levels of PRL and IGFBP1 were significantly decreased by treatment with OP or NP. The amounts of PRL and IGFBP1 were also significantly decreased by treatment with OP or NP. The patterns of PRL and IGFBP1 secretion into medium were consistent with their expression patterns. The findings indicate that OP or NP may disrupt the decidualization of endometrial stromal cells and eventually affect the reproductive health of women., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Salmonella enterica subsp. enterica serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid (FT) and substantial economic loss in Korea due to egg drop syndrome and mortality. Despite the extensive use of vaccines, FT still occurs in the field. Therefore, the emergence of more pathogenic SG or the recovered pathogenicity of a vaccine strain has been suspected. SpvB, an ADP-ribosyl transferase, is a major pathogenesis determinant, and the length of the polyproline linker (PPL) of SpvB affects pathogenic potency. SG strains accumulate pseudogenes in their genomes during host adaptation, and pseudogene profiling may provide evolutionary information. In this study, we found that the PPL length of Korean SG isolates varied from 11 to 21 prolines and was longer than that of a live vaccine strain, SG 9R (9 prolines). According to growth competition in chickens, the growth of an SG isolate with a PPL length of 17 prolines exceeded that of an SG isolate with a PPL length of 15 prolines. We investigated the pseudogenes of the field isolates, SG 9R and reference strains in GenBank by resequencing and comparative genomics. The pseudogene profiles of the field isolates were notably different from those of the foreign SG strains, and they were subdivided into 7 pseudogene subgroups. Collectively, the field isolates had gradually evolved by changing PPL length and acquiring additional pseudogenes. Thus, the characterization of PPL length and pseudogene profiling may be useful to understand the molecular evolution of SG and the epidemiology of FT., (Copyright © 2019. Published by Elsevier B.V.)

Staphylococcus aureus is the major pathogen leading to bovine mastitis globally while livestock-associated methicillin resistant S. aureus (LA-MRSA) has become a potential threat to public health. MRSA from bovine mastitis is not common but a methicillin susceptible S. aureus (MSSA) genotype, rpoB sequence type (RST)10-2 (RST10-2), is prevalent in Korea. To date, many genomic sequences from S. aureus have been elucidated, but the complete genome sequences of RST10-2 MSSA from bovine mastitis has never been reported. In this study, we determined the complete genome sequence of two RST10-2 MSSA that differ from each other in staphylococcal protein A and molecular prophage types [PMB64-1 (t2489/ mPPT0) and PMB81-4 (t127/mPPT1-2-3)] and conducted a comparative genomics study. The genomic sequences of PMB64-1 and PMB81-4 were more homologous to the representative human RST10-2 strains (MSSA476, MW2 etc.) compared to other RSTs. Most of them shared five common pseudogenes, along with high amino acid identity of four variable virulence genes that were identified in this study. However, PMB64-1 and PMB81-4 acquired different strainspecific pseudogenes and mobile genetic elements than the human strains. The unique pseudogene profile and high identity of the virulence genes were verified in RST10-2 field strains from bovine mastitis. Thus, bovine mastitic RST10-2 MSSA may have an evolutionary relationship with the human RST10-2 community-associated (CA) MSSA and CA-MRSA strains but may have adapted to cows.

Urologists were early adopters of minimally invasive, specifically robotic, techniques for cancer surgery. The current trends show increasing adoption of robotic surgery for renal, bladder, and prostate cancer. Several randomized controlled trials show that robotic urologic surgery has outcomes that are at least as good as, if not superior to, open surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Paediatric liver allografts sometimes are allocated to adult recipients when there are no suitable paediatric recipients on the waiting list. However, debate exits regarding the reported outcomes of liver transplants using such small grafts., Methods: Records from adult patients undergoing liver transplantation between February 2010 and January 2016 who received whole grafts from paediatric (≤ 13 years) donors or ideal deceased adult (18-35 years) donors were reviewed. Patient and graft survival, post-transplant liver function, and complications between the two groups were compared., Results: The baseline characteristics were comparable, except that the paediatric donor allografts had smaller size. The 3-month, 1-year, and 3-year rates of patient survival were 91.3%, 85.2%, and 85.2% in the paediatric donor group and 93.4%, 88.9%, and 85.0% in the adult donor group (P = 0.947), respectively. One patient receiving a paediatric allograft developed small-for-size liver syndrome post-transplantation. There was no difference in primary non-function, early allograft dysfunction, biliary complications, vascular complications, or infection between the two groups., Conclusion: Our study indicates that using paediatric donor livers in well-selected adult recipients is a safe procedure, considering there was no suitable paediatric recipient. However, the risk of portal hyperperfusion should be considered in clinical cases such as size-mismatched transplants., (Copyright © 2018. Published by Elsevier Masson SAS.)