Electoral rewards for political grandstanding.

Many assumed that legislators send political messages or even grandstand in expectation of gaining electoral rewards. However, largely due to a lack of proper data and measurements, this assumption has not been tested. Publicized committee hearings provide a unique environment to consistently observe changes in legislators' speech patterns and test this assumption. Using House committee hearing transcripts from 1997 to 2016 and Grandstanding Scores-which capture the intensity of political messages conveyed in members' statements in hearings-I find that an increase in a member's messaging efforts in a given Congress leads to increased vote share in the following election. This suggests that legislators' grandstanding remarks, often regarded as cheap talk, can be an effective electoral strategy. Additional findings suggest that PAC donors respond differently to members' grandstanding behavior. Specifically, while voters react to members' grandstanding positively but are ignorant about their legislative effectiveness, PAC donors are unmoved by members' grandstanding behaviors and reward members' effective law-making activities instead. These asymmetric reactions from voters and donors may provide members with a twisted incentive to appeal to voters merely by making impressive, political speeches while legislating in favor of organized interests, which raises concerns about how representative democracy works.

Clinical significance of serum-derived exosomal PD-L1 expression in patients with advanced pancreatic cancer.

BACKGROUND: Interactions between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) lead to immune evasion in various tumors and are associated with poor prognosis in patients with pancreatic cancer; however, the roles of PD-L1-containing exosomes in pancreatic cancer is poorly understood. Here, we investigated the correlation between circulating exosomal PD-L1 (exoPD-L1) and PD-L1 expression in tumor tissue, and survival outcomes in patients with advanced PDAC. METHODS: Exosomes were derived from pre-treatment serum samples isolated using ExoQuick kit from 77 patients with advanced pancreatic cancer. Exosomal PD-L1 (exoPD-L1) was detected by enzyme-linked immunosorbent assay, and matched tumor tissues PD-L1 expression were evaluated by PD-L1 immunohistochemistry (22C3) assay, described with combined positive score. Cutoff value of exoPD-L1 for survival was assessed with receiver operating characteristic curve analysis. Kaplan-Meier analysis was performed to obtain median overall survival (OS), and hazard ratio was estimated using a stratified Cox regression model. RESULTS: The median exoPD-L1 serum concentration was 0.16 pg/mg, with undetected levels in seven patients. ExoPD-L1 levels were significantly higher in patients with systemic disease than in those with locally advanced disease (p = 0.023). There was a significantly higher proportion of elevated exoPD-L1 levels in patients with positive PD-L1 expression compared to patients with negative PD-L1 expression (p = 0.001). Patients were classified into groups with low and high exoPD-L1 levels using ROC curve-derived cutoffs (0.165 pg/mg; area under the curve, 0.617; p = 0.078). At a median follow-up of 8.39 months, the median OS was 13.2 (95% CI, 8.17-18.3) and 6.36 months (95% CI, 3.27-9.45) in the low and high exoPD-L1 groups, respectively (HR = 0.61; 95% CI, 0.35-1.04; p = 0.059). ExoPD-L1 levels did not affect the proportion of CD8+CD69+ effector cytotoxic T cells in either of the groups (p = 0.166). CONCLUSIONS: The serum-derived exoPD-L1 levels were higher in metastatic pancreatic cancer than locally advanced disease. Collectively, higher serum exoPD-L1 levels in patients with advanced pancreatic cancer suggested worse survival outcomes and may have clinical implications.

Chronic intermittent hypoxia impacts the olfactory nervous system in an age-dependent manner: pilot study.

PURPOSE: Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse during sleep, which induces chronic intermittent hypoxia (CIH). CIH results in low-grade inflammation, sympathetic overactivity, and oxidative stress. Nevertheless, it remains unclear how exposure to CIH affects olfaction. The purpose of this study was, therefore, to investigate the cytotoxic effects of CIH exposure on mouse olfactory epithelium and the underlying pathophysiology involved. METHODS: Mice were randomly divided into four groups: Youth mouse (You) + room air (RA), You + intermittent hypoxia (IH), Elderly mouse (Eld) + RA, and Eld + IH (n = 6 mice/group). Mice in the two hypoxia groups were exposed to CIH. The control condition involved exposure to room air (RA) for 4 weeks. Olfactory neuroepithelium was harvested for histologic examination, gene ontology analysis, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. RESULTS: Based on qRT-PCR analysis, olfactory marker protein (OMP), Olfr1507, ADCY3, and GNAL mRNA levels were lower, whereas NGFR, CNPase, NGFRAP1, NeuN, and MAP-2 mRNA levels were higher in the You + IH group than in the You + RA group. Olfactory receptor-regulated genes, neurogenesis-related genes and immunohistochemical results were altered in nasal neuroepithelium under CIH exposure. CONCLUSIONS: Based on genetic and cytologic analysis, CIH impacted the olfactory neuroepithelium in an age-dependent manner. Our findings suggest that CIH-induced damage to the olfactory neuroepithelium may induce more severe change in the youth than in the elderly.

Risk factors for heel pressure injury in cardiovascular intensive care unit patients.

This study analyzed the risk factors for heel pressure injury in cardiovascular intensive care unit patients with the aim of laying the groundwork for preventive nursing interventions. We conducted a retrospective case-control study of 92 patients who were admitted to the cardiovascular surgical or medical intensive care unit of a university hospital in South Korea between January and December 2017. Of these patients, 31 and 61 were included to the heel pressure injury group and the non-heel pressure injury group, respectively. Data on their demographic, disease-related, and intensive care unit treatment characteristics, as well as the degree of pressure injury, were collected from the hospital's electronic medical records using a standardized form. Cardiac surgery (P < .001), operation time (P = .001), use of a mechanical ventilator (P < .001), use of vasoconstrictors (P < .001), use of sedative drugs (P < .001), and extracorporeal membrane oxygenation treatment (P < .001) were identified as significant risk factors for heel pressure injury. A total of 22 patients (71%) from the heel pressure injury group developed deep tissue injury, and 16 patients (51.6%) who received extracorporeal membrane oxygenation treatment developed heel pressure injury.

Differential Contribution of RNA Interference Components in Response to Distinct Fusarium graminearum Virus Infections.

The mechanisms of RNA interference (RNAi) as a defense response against viruses remain unclear in many plant-pathogenic fungi. In this study, we used reverse genetics and virus-derived small RNA profiling to investigate the contributions of RNAi components to the antiviral response against Fusarium graminearum viruses 1 to 3 (FgV1, -2, and -3). Real-time reverse transcription-quantitative PCR (qRT-PCR) indicated that infection of Fusarium graminearum by FgV1, -2, or -3 differentially induces the gene expression of RNAi components in F. graminearum Transcripts of the DICER-2 and AGO-1 genes of F. graminearum (FgDICER-2 and FgAGO-1) accumulated at lower levels following FgV1 infection than following FgV2 or FgV3 infection. We constructed gene disruption and overexpression mutants for each of the Argonaute and dicer genes and for two RNA-dependent RNA polymerase (RdRP) genes and generated virus-infected strains of each mutant. Interestingly, mycelial growth was significantly faster for the FgV1-infected FgAGO-1 overexpression mutant than for the FgV1-infected wild type, while neither FgV2 nor FgV3 infection altered the colony morphology of the gene deletion and overexpression mutants. FgV1 RNA accumulation was significantly decreased in the FgAGO-1 overexpression mutant. Furthermore, the levels of induction of FgAGO-1, FgDICER-2, and some of the FgRdRP genes caused by FgV2 and FgV3 infection were similar to those caused by hairpin RNA-induced gene silencing. Using small RNA sequencing analysis, we documented different patterns of virus-derived small interfering RNA (vsiRNA) production in strains infected with FgV1, -2, and -3. Our results suggest that the Argonaute protein encoded by FgAGO-1 is required for RNAi in F. graminearum, that FgAGO-1 induction differs in response to FgV1, -2, and -3, and that FgAGO-1 might contribute to the accumulation of vsiRNAs in FgV1-infected F. graminearumIMPORTANCE To increase our understanding of how RNAi components in Fusarium graminearum react to mycovirus infections, we characterized the role(s) of RNAi components involved in the antiviral defense response against Fusarium graminearum viruses (FgVs). We observed differences in the levels of induction of RNA silencing-related genes, including FgDICER-2 and FgAGO-1, in response to infection by three different FgVs. FgAGO-1 can efficiently induce a robust RNAi response against FgV1 infection, but FgDICER genes might be relatively redundant to FgAGO-1 with respect to antiviral defense. However, the contribution of this gene in the response to the other FgV infections might be small. Compared to previous studies of Cryphonectria parasitica, which showed dicer-like protein 2 and Argonaute-like protein 2 to be important in antiviral RNA silencing, our results showed that F. graminearum developed a more complex and robust RNA silencing system against mycoviruses and that FgDICER-1 and FgDICER-2 and FgAGO-1 and FgAGO-2 had redundant roles in antiviral RNA silencing.

A novel PI3K/mTOR dual inhibitor, CMG002, overcomes the chemoresistance in ovarian cancer.

OBJECTIVE: Ovarian cancer is the leading cause of gynecologic-related mortality worldwide. Despite successful initial treatment, overall survival rates are very low because tumors develop resistance to chemotherapeutic drugs. The PI3K/mTOR pathway is a key signaling pathway involved in drug resistance of ovarian cancer cells. The aim of this study was to examine the effect of a newly developed PI3K/mTOR dual inhibitor, CMG002, on chemoresistant ovarian cancer cells. METHODS: We examined the effects of CMG002, and its synergistic effects when combined with paclitaxel or cisplatin, on cell viability, cell cycle arrest, and apoptosis of PTX-resistant SKpac17 or cisplatin-resistant A2780cis ovarian cancer cells in vitro. Western blot analysis was performed to assess expression of PI3K, p-mTOR, p-Akt, p-S6, Bim, and caspase-3. In vivo studies were carried out in a xenograft mouse model, followed by TUNEL and immunohistochemical staining of excised tumor tissue. RESULTS: CMG002 showed marked toxicity against chemoresistant ovarian cancer cells and re-sensitized these cells to chemotherapeutic agents by suppressing cell proliferation and inducing G1 cell cycle arrest and apoptosis. In vivo xenograft studies revealed that treatment with CMG002, either alone or in combination with paclitaxel or cisplatin, led to a marked reduction in tumor growth. CMG002 caused marked suppression of mTOR (Ser2448), Akt (Ser473), Akt (Thr308), and S6 (Ser235/236) phosphorylation, both in vitro and in vivo. CONCLUSION: Taken together, CMG002, a very potent PI3K/mTOR dual inhibitor, induced cytotoxicity in chemoresistant ovarian cancer cells, suggesting that this novel inhibitor might be a new therapeutic strategy for chemoresistant ovarian cancer.

The correlation between conventional coagulation tests and thromboelastography in each phase of liver transplantation.

INTRODUCTION: Thromboelastography (TEG) is gaining increasing acceptance in liver transplantation (LT) with conventional coagulation tests (CCTs) such as prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin III (ATIII), platelet count (PLT), and fibrinogen concentration. The purpose of this study was to evaluate the clinical utility of TEG in LT and investigate the correlation between TEG and CCT values during each phase of LT. MATERIALS AND METHODS: Medical records of patients who underwent deceased donor LT at a single, university hospital between October 2010 and July 2015 were retrospectively reviewed. Blood samples were obtained at each phase of LT (pre-anhepatic, anhepatic, and neo-hepatic phase) according to our institutional LT protocol and utilized for analysis of TEG and CCTs. The Spearman correlation coefficient between TEG and CCT values were obtained. RESULTS: During the pre-anhepatic phase, the reaction time (R), PT, and aPTT did not correlate with each other, but demonstrated a negative correlation with PLT. Clot formation time (K) demonstrated a similar correlation with R and a negative correlation with fibrinogen. The maximal amplitude (MA) and α-angle (α) were positively correlated with PLT and fibrinogen and inversely correlated with aPTT. During the anhepatic phase, MA was significantly correlated with PLT and inversely correlated with aPTT; other parameters had weak or indistinct correlation. During the neo-hepatic phase, R and K were significantly correlated with aPTT and inversely correlated with PLT and fibrinogen. A correlation of MA and α with PLT, aPTT, and fibrinogen was also observed. Clot lysis at 30 minutes and estimated percent lysis were inversely correlated with levels of ATIII and fibrinogen. CONCLUSIONS: Conventional coagulation tests and TEG show particularly poor comparability during the anhepatic period of liver transplantation. TEG can be most reliable in the anhepatic phase, during which dynamic hemostatic changes occur.

The influence of rapid eye movement sleep deprivation on nociceptive transmission and the duration of facial allodynia in rats: a behavioral and Fos immunohistochemical study.

BACKGROUND: Disrupted sleep is associated with a reciprocal influence on headaches and is one of the contributing factors in the process of chronicity. The goal of the present study was to investigate the influence of sleep on headaches using animal rapid eye movement (REM) sleep deprivation and supradural capsaicin infusion models. METHOD: Sprague-Dawley rats underwent REM sleep deprivation (REMSD) for 96 h. The sensory threshold to mechanical stimuli, assessed by the von Frey monofilament test, was measured during the REMSD period. Additionally, the Fos protein expression level was measured in the trigeminocervical complex, periaqueductal gray, and hypothalamus. Following supradural infusion of capsaicin, we evaluated the duration of facial allodynia for 28 days after REMSD. RESULTS: After REMSD, the sensory threshold to mechanical stimuli was significantly decreased (p < 0.01) and Fos-positivity in the posterior (p = 0.010) and dorsomedial hypothalamus (p = 0.024), ventrolateral periaqueductal gray (p = 0.016), and superficial layer of the trigeminocervical complex (p = 0.019) were significantly increased. The duration of facial allodynia induced by supradural capsaicin infusion was significantly longer in the REM sleep deprivation and capsaicin infusion group (Day 10 PSD vs. Day 25 PSD). CONCLUSION: The present study demonstrates that REM sleep deprivation increased nociceptive transmission from trigeminal nerve endings. Furthermore, it suggests that sleep deprivation may contribute to the chronicity of facial allodynia.

Herbal formula SC-E1 suppresses lipopolysaccharide-stimulated inflammatory responses through activation of Nrf2/HO-1 signaling pathway in RAW 264.7 macrophages.

BACKGROUND: SC-E1 is a novel herbal formula consisting of five oriental medicinal herbs used frequently in traditional herbal medicine for the treatment of inflammatory diseases in Korea. This study examined the effects of SC-E1 on lipopolysaccharide (LPS)-stimulated macrophages and the molecular mechanism involved. METHODS: The cytotoxic effect of the SC-E1 extract was evaluated in RAW 264.7 cells by MTT assay. The effects of SC-E1 on the free radical scavenging and generation of intracellular reactive oxygen species were measured using DPPH and DCFH-DA, respectively. The effects of SC-E1 on the production of pro-inflammatory cytokines, inflammatory mediators, and related products were determined by ELISA and western blotting. The molecular mechanism and the nuclear translocation of nuclear factor-kappa B (NF-κB) and NF-E2-related factor 2 (Nrf2) were examined by western blot analysis and immunocytochemistry. RESULTS: SC-E1 exhibited strong anti-oxidant activity and inhibited LPS-induced NO secretion as well as iNOS expression and the production of pro-inflammatory cytokines, without affecting the cell viability. SC-E1 also suppressed the LPS-induced NF-κB activation and the mitogen-activated protein kinase (MAPK) pathway. Moreover, SC-E1 induced heme oxygenase-1 (HO-1) expression via the nuclear translocation of Nrf2. The inhibitory effects of SC-E1 on the production of pro-inflammatory cytokines were abrogated by treatment with SnPP, an HO-1 inhibitor. CONCLUSION: These results suggest that SC-E1 exerts its anti-oxidant and anti-inflammatory effects through the inhibition of NF-κB and MAPK as well as Nrf2-mediated HO-1 induction in macrophages. These findings provide evidences for SC-E1 to be considered as a new prescription for treating inflammatory diseases.

Investigation of relative metabolic changes in the organs and plasma of rats exposed to X-ray radiation using HR-MAS (1)H NMR and solution (1)H NMR.

Excess exposure to ionizing radiation generates reactive oxygen species and increases the cellular inflammatory response by modifying various metabolic pathways. However, an investigation of metabolic perturbations and organ-specific responses based on the amount of radiation during the acute phase has not been conducted. In this study, high-resolution magic-angle-spinning (HR-MAS) NMR and solution NMR-based metabolic profiling were used to investigate dose-dependent metabolic changes in multiple organs and tissues--including the jejunum, spleen, liver, and plasma--of rats exposed to X-ray radiation. The organs, tissues, and blood samples were obtained 24, 48, and 72 h after exposure to low-dose (2 Gy) and high-dose (6 Gy) X-ray radiation and subjected to metabolite profiling and multivariate analyses. The results showed the time course of the metabolic responses, and many significant changes were detected in the high-dose compared with the low-dose group. Metabolites with antioxidant properties showed acute responses in the jejunum and spleen after radiation exposure. The levels of metabolites related to lipid and protein metabolism were decreased in the jejunum. In addition, amino acid levels increased consistently at all post-irradiation time points as a consequence of activated protein breakdown. Consistent with these changes, plasma levels of tricarboxylic acid cycle intermediate metabolites decreased. The liver did not appear to undergo remarkable metabolic changes after radiation exposure. These results may provide insight into the major metabolic perturbations and mechanisms of the biological systems in response to pathophysiological damage caused by X-ray radiation.

Comparison of immune responses to a killed bivalent whole cell oral cholera vaccine between endemic and less endemic settings.

Studies on safety, immunogenicity and efficacy of the killed, bivalent whole cell oral cholera vaccine (Shanchol) have been conducted in historically endemic settings of Asia. Recent cholera vaccination campaigns in Haiti and Guinea have also demonstrated favourable immunogenicity and effectiveness in nonendemic outbreak settings. We performed a secondary analysis, comparing immune responses of Shanchol from two randomised controlled trials performed in an endemic and a less endemic area (Addis Ababa) during a nonoutbreak setting. While Shanchol may offer some degree of immediate protection in primed populations living in cholera endemic areas, as well as being highly immunogenic in less endemic settings, understanding the characteristics of immune responses in each of these areas is vital in determining ideal dosing strategies that offer the greatest public health impact to populations from areas with varying degrees of cholera endemicity.

Revisiting typhoid fever surveillance in low and middle income countries: lessons from systematic literature review of population-based longitudinal studies.

BACKGROUND: The control of typhoid fever being an important public health concern in low and middle income countries, improving typhoid surveillance will help in planning and implementing typhoid control activities such as deployment of new generation Vi conjugate typhoid vaccines. METHODS: We conducted a systematic literature review of longitudinal population-based blood culture-confirmed typhoid fever studies from low and middle income countries published from 1(st) January 1990 to 31(st) December 2013. We quantitatively summarized typhoid fever incidence rates and qualitatively reviewed study methodology that could have influenced rate estimates. We used meta-analysis approach based on random effects model in summarizing the hospitalization rates. RESULTS: Twenty-two papers presented longitudinal population-based and blood culture-confirmed typhoid fever incidence estimates from 20 distinct sites in low and middle income countries. The reported incidence and hospitalizations rates were heterogeneous as well as the study methodology across the sites. We elucidated how the incidence rates were underestimated in published studies. We summarized six categories of under-estimation biases observed in these studies and presented potential solutions. CONCLUSIONS: Published longitudinal typhoid fever studies in low and middle income countries are geographically clustered and the methodology employed has a potential for underestimation. Future studies should account for these limitations.

Amomum cardamomum L. ethyl acetate fraction protects against carbon tetrachloride-induced liver injury via an antioxidant mechanism in rats.

BACKGROUND: Medicinal herb-derived drug development has become important in the relief of liver pathology. Amomun cardamomum is traditionally used therapeutically in Korea to treat various human ailments including dyspepsia, hiccupping, and vomiting. We investigated to assess the protective effect of A. cardamomum on carbon tetrachloride (CCl4)-induced liver damage through antioxidant activity in hepatic tissues of Sprague-Dawley rats. METHODS: Antioxidant properties of different fractions from A. cardamomum from ethanol extracts were evaluated by an in vitro free radical scavenging systems. The protective effect of the ethyl acetate fraction from A. cardamomum (EAAC) against CCl4-induced cytotoxicity was determined by a cell viability assay using HepG2 hepatocarcinoma cells. In vivo study, the influence of EAAC concentrations of 100 and 200 mg/kg following CCl4-induced hepatic injury was assessed. Serum levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and alkaline phosphatase (ALP) were determined, as was lipid peroxidation (malondialdehyde, MDA). Effect of EAAC on liver detoxification enzymes including superoxide dismutase (SOD), total glutathione (GSH), and glutathione S-transferase (GST) activity was measured in rat liver homogenates. Liver cytochrome P450 (CYP2E1) expression level was determined by quantification of mRNA. RESULTS: Phytochemical analysis of A. cardamomum indicated that EAAC was enriched in total polyphenol and total flavonoid. Most of the tannins were confined to the hexane fraction. Hepatoprotective properties of EAAC were evident, with significantly reduced serum levels of GOT, GPT, and ALP compared with the control group. Improved hepatic antioxidant status was evident by increased SOD, GSH, and GST enzymes in rat liver tissue. Liver lipid peroxidation induced by CCl4 was apparent by increased intracellular MDA level. EAAC suppressed lipid peroxidation as evidenced by the significant decrease in MDA production. Expression of CYP2E1 was also significantly decreased at the higher concentration of EAAC, indicating the hepatoprotective efficacy of EAAC on acute liver damage. CONCLUSION: These results indicated that EAAC has a significant hepatoprotective activity on CCl4-induced acute hepatic injury in rats, which might be derived from its antioxidant properties and CYP2E1 downregulation.

The Effects of Mind Subtraction Meditation on Depression, Social Anxiety, Aggression, and Salivary Cortisol Levels of Elementary School Children in South Korea.

This study analyzed the effects of a school-based mind subtraction meditation program on depression, social anxiety, aggression, and salivary cortisol levels of 42 elementary school children in South Korea. The research design was a nonequivalent group comparison with pretest and post-test. The experimental group was given 8weeks of the meditation program. The results showed social anxiety, aggression, and salivary cortisol levels were significantly lowered in the experimental group. This demonstrated that the school-based mind subtraction meditation program could be effective in improving psychosocial and behavioral aspects of mental health in elementary school children.

The global regulator GacS regulates biofilm formation in Pseudomonas chlororaphis O6 differently with carbon source.

An aggressive root colonizer, Pseudomonas chlororaphis O6 produces various secondary metabolites that impact plant health. The sensor kinase GacS is a key regulator of the expression of biocontrol-related traits. Biofilm formation is one such trait because of its role in root surface colonization. This paper focuses on the effects of carbon source on biofilm formation. In comparison with the wild type, a gacS mutant formed biofilms at a reduced level with sucrose as the major carbon source but at much higher level with mannitol in the defined medium. Biofilm formation by the gacS mutant occurred without phenazine production and in the absence of normal levels of acyl homoserine lactones, which promote biofilms with other pseudomonads. Colonization of tomato roots was similar for the wild type and gacS mutant, showing that any differences in biofilm formation in the rhizosphere were not of consequence under the tested conditions. The reduced ability of the gacS mutant to induce systemic resistance against tomato leaf mold and tomato gray mold was consistent with a lack of production of effectors, such as phenazines. These results demonstrated plasticity in biofilm formation and root colonization in the rhizosphere by a beneficial pseudomonad.

The Role of Pretreatment Serum Interleukin 6 in Predicting Short-Term Mortality in Patients with Advanced Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its aggressive progression and dismal survival rates, with this study highlighting elevated interleukin 6 (IL-6) levels in patients as a key marker of increased disease severity and a potential prognostic indicator. Analyzing pre-treatment serum from 77 advanced PDAC patients via ELISA, the research determined optimal cutoff values for IL-6 and the IL-6:sIL-6Rα ratio using receiver operating characteristic curve analysis, which then facilitated the division of patients into low and high IL-6 groups, showing significantly different survival outcomes. Notably, high IL-6 levels correlated with adverse features such as poorly differentiated histology, higher tumor burden, and low albumin levels, indicating a stronger likelihood of poorer prognosis. With a median follow-up of 9.28 months, patients with lower IL-6 levels experienced markedly better median overall survival and progression-free survival than those with higher levels, underscoring IL-6's role in predicting disease prognosis. Multivariate analysis further confirmed IL-6 levels, alongside older age, and elevated neutrophil-to-lymphocyte ratio, as predictors of worse outcomes, suggesting that IL-6 could be a critical biomarker for tailoring treatment strategies in advanced PDAC, warranting further investigation into its role in systemic inflammation and the tumor microenvironment.

Separation of High-Purity C2H2 from Binary C2H2/CO2 Using Robust Al-Based MOFs Comprising Nitrogen-Containing Heterocyclic Dicarboxylate.

In this study, three nitrogen-containing aluminum-based metal-organic frameworks (Al-MOFs), namely, CAU-10pydc, MOF-303, and KMF-1, were investigated for the efficient separation of a C2H2/CO2 gas mixture. Among these three Al-MOFs, KMF-1 demonstrated the highest selectivity for C2H2/CO2 separation (6.31), primarily owing to its superior C2H2 uptake (7.90 mmol g-1) and lower CO2 uptake (2.82 mmol g-1) compared to that of the other two Al-MOFs. Dynamic breakthrough experiments, using an equimolar binary C2H2/CO2 gas mixture, demonstrated that KMF-1 achieved the highest separation performance. It yielded 3.42 mmol g-1 of high-purity C2H2 (>99.95%) through a straightforward desorption process under He purging at 298 K and 1 bar. To gain insights into the distinctive characteristics of the pore surfaces of structurally similar CAU-10pydc and KMF-1, we conducted computational simulations using canonical Monte Carlo and dispersion-corrected density functional theory methods. These simulations revealed that the secondary amine (C2N-H) groups in KMF-1 played a more significant role in differentiating between C2H2 and CO2 compared to that of the N atoms in CAU-10pydc and MOF-303. Consequently, KMF-1 emerged as a promising adsorbent for the separation of high-purity C2H2 from binary C2H2/CO2 gas mixtures.

Cholera and diarrheal diseases in Cuamba District, Niassa Province, Mozambique: Systematic healthcare facility-based surveillance strengthening, characteristics of suspected cholera and diarrheal patients, and incidence of diarrheal diseases.

BACKGROUND: Mozambique is one of the countries in Africa that is continuously at risk of cholera outbreaks due to poor sanitation, hygiene, and limited access to potable water in some districts. The Mozambique Cholera Prevention and Surveillance (MOCA) project was implemented in Cuamba District, Niassa Province to prevent and control cholera outbreaks through a preemptive cholera vaccination, strengthened surveillance system for cholera and diarrheal diseases, and better understanding of cholera-related healthcare seeking behavior of local populations, which may further guide the national cholera control and prevention strategies. This article presents the surveillance component of the MOCA project. METHODOLOGY/PRINCIPAL FINDINGS: A prospective healthcare facility (HCF)-based surveillance of cholera and diarrheal disease was conducted in six HCFs in the District of Cuamba from March 2019 to December 2020. A systematic surveillance procedure has been put in place with capacity building in selected sentinel HCFs and a basic microbiology laboratory established on-site. Patients presenting with suspected cholera or other diarrheal symptoms were eligible for enrollment. Clinical data and rectal swab samples were collected for laboratory confirmation of Vibrio Cholerae and other pathogens. A total of 419 eligible patients from six HCFs were enrolled. The median age was 19.8 years with a similar age distribution between sentinel sites. The majority were patients who exhibited diarrhea symptoms not suspected of cholera (88.8%; n = 410). Among those, 59.2% (210/397) were female and 59.9% (235/392) were 15 years and above. There were 2 cholera cases, coming outside of the catchment area. The incidence of diarrheal diseases ranged from 40-103 per 100,000 population. No Vibrio cholerae was isolated among surveillance catchment population and Escherichia coli spp. (82/277; 29.6%) was the most common pathogen isolated. CONCLUSION/SIGNIFICANCE: Efforts were made to strengthen the systematic surveillance of suspected cholera with standardised patient screening, enrolment, and diagnostics. The first basic microbiology laboratory in Niassa Province established in Cuamba District under the MOCA project needs to be integrated into the national network of laboratories for sustainability. No reports of laboratory confirmed cholera cases from the surveillance catchment area may be highly related to the pre-emptive oral cholera vaccine (OCV) mass vaccination campaign conducted in 2018 and the use of drugs by local populations prior to visiting the sentinel HCFs. Continued systematic cholera surveillance is needed to closely monitor the cholera endemicity and epidemics, and further evaluate the long-term impact of this vaccination. High incidence of diarrheal illnesses needs to be addressed with improved water, sanitation, and hygiene (WaSH) conditions in Cuamba District. Efforts integrated with the prioritization of prevention measures are fundamental for the control of cholera in the country.

The GacS-regulated sigma factor RpoS governs production of several factors involved in biocontrol activity of the rhizobacterium Pseudomonas chlororaphis O6.

Pseudomonas chlororaphis O6 possesses many beneficial traits involved in biocontrol of plant diseases. In this paper, we examined the effect of a mutation in rpoS encoding a stress-related alternative sigma factor to better understand the regulation of these traits. Biochemical studies indicated that production of acyl homoserine lactones was altered and phenazine was increased in the P. chlororaphis O6 rpoS mutant. The rpoS mutation reduced hydrogen cyanide levels, but the rpoS mutant still displayed a level of in vitro antifungal activity against Fusarium graminearum and Alternaria alternata. Tomato root colonization by the rpoS mutant was lower than that by the wild type at 5, 7, and 13 days after inoculation. The rpoS mutant was less effective than the wild type in induction of systemic resistance to two foliar pathogens after root inoculation of the tomato plants. Our findings demonstrate that the stationary-phase sigma factor RpoS regulates production of several key factors involved in the biocontrol potential of P. chlororaphis O6, some independently of the global regulator GacS.

Genome-wide association study of lung cancer in Korean non-smoking women.

Lung cancer in never-smokers ranks as the seventh most common cause of cancer death worldwide, and the incidence of lung cancer in non-smoking Korean women appears to be steadily increasing. To identify the effect of genetic polymorphisms on lung cancer risk in non-smoking Korean women, we conducted a genome-wide association study of Korean female non-smokers with lung cancer. We analyzed 440,794 genotype data of 285 cases and 1,455 controls, and nineteen SNPs were associated with lung cancer development (P < 0.001). For external validation, nineteen SNPs were replicated in another sample set composed of 293 cases and 495 controls, and only rs10187911 on 2p16.3 was significantly associated with lung cancer development (dominant model, OR of TG or GG, 1.58, P = 0.025). We confirmed this SNP again in another replication set composed of 546 cases and 744 controls (recessive model, OR of GG, 1.32, P = 0.027). OR and P value in combined set were 1.37 and < 0.001 in additive model, 1.51 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model. The effect of this SNP was found to be consistent only in adenocarcinoma patients (1.36 and < 0.001 in additive model, 1.49 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model). Furthermore, after imputation with HapMap data, we found regional significance near rs10187911, and five SNPs showed P value less than that of rs10187911 (rs12478012, rs4377361, rs13005521, rs12475464, and rs7564130). Therefore, we concluded that a region on chromosome 2 is significantly associated with lung cancer risk in Korean non-smoking women.