bluuebunny/crossref_metadata_2025_split huggingface dataset:
DC‐CIK cells derived from ovarian cancer patient menstrual blood activate the TNFR1‐ASK1‐AIP1 pathway to kill autologous ovarian cancer stem cells
Authors: Qin Wenxing , Xiong Ying , Chen Juan , Huang Yongyi , Liu Te 
Published: March 2018

AbstractOvarian cancer stem cells (OCSCs) are highly carcinogenic and have very strong resistance to traditional chemotherapeutic drugs; therefore, they are an important factor in ovarian cancer metastasis and recurrence. It has been reported that dendritic cell (DC)‐cytokine‐induced killer (CIK) cells have significant killing effects on all cancer cells across many systems including the blood, digestive, respiratory, urinary and reproductive systems. However, whether DC‐CIK cells can selectively kill OCSCs is currently unclear. In this study, we collected ovarian cancer patient menstrual blood (OCPMB) samples to acquire mononuclear cells and isolated DC‐CIK cells in vitro. In addition, autologous CD44+/CD133+ OCSCs were isolated and used as target cells. The experimental results showed that when DC‐CIK cells and OCSCs were mixed and cultured in vitro at ratios of 5:1, 10:1 and 50:1, the DC‐CIK cells killed significant amounts of OCSCs, inhibited their invasion in vitro and promoted their apoptosis. The qPCR and Western blot results showed that DC‐CIK cells stimulated high expression levels and phosphorylation of TNFR1, ASK1, AIP1 and JNK in OCSCs through the release of TNF‐α. After the endogenous TNFR1 gene was knocked out in OCSCs using the CRISPR/Cas9 technology, the killing function of DC‐CIK cells on target OCSCs was significantly attenuated. The results of the analyses of clinical samples suggested that the TNFR1 expression level was negatively correlated with ovarian cancer stage and prognosis. Therefore, we innovatively confirmed that DC‐CIK cells derived from OCPMB could secret TNF‐α to activate the expression of the TNFR1‐ASK1‐AIP1‐JNK pathway in OCSCs and kill autologous OCSCs.
Use of Antiepileptic Drugs and Dementia Risk—an Analysis of Finnish Health Register and German Health Insurance Data
Authors: Taipale Heidi , Gomm Willy , Broich Karl , Maier Wolfgang , Tolppanen Anna‐Maija , Tanskanen Antti , Tiihonen Jari , Hartikainen Sirpa , Haenisch Britta 
Published: March 2018

ObjectivesTo evaluate the association between regular antiepileptic drug (AED) use and incident dementia.DesignCase‐control analysis.SettingFinnish public health register and German health insurance data.ParticipantsIndividuals with dementia of any type (German data, N=20,325) and Alzheimer's disease (AD; Finnish data, N=70,718) were matched with up to four control persons without dementia.MeasurementsWe analyzed the association between regular AED use and dementia. To address potential protopathic bias, a lag time of 2 years between AED use and dementia diagnosis was introduced. Odds ratios (ORs) were calculated by applying conditional logistic regression, adjusted for potential confounding factors such as comorbidities and polypharmacy.ResultsRegular AED use was more frequent in individuals with dementia than controls. Regular use of AEDs was associated with a significantly greater risk of incident dementia (adjusted OR=1.28, 95% confidence interval (CI)=1.14–1.44) and AD (adjusted OR=1.15, 95% CI=1.09–1.22) than no AED use. We also detected a trend toward greater risk of dementia with higher exposure. When AEDs with and without known cognitive adverse effects (CAEs) were compared, a significantly greater risk of dementia was observed for substances with known CAEs (dementia: OR=1.59, 95% CI=1.36–1.86; AD: OR=1.19, 95% CI=1.11–1.27).ConclusionAEDs, especially those with known CAEs, may contribute to incident dementia and AD in older persons.
The Breath‐Hold Acceleration Index: A New Method to Evaluate Cerebrovascular Reactivity using Transcranial Doppler
Authors: Alwatban Mohammed , Truemper Edward J. , Al‐rethaia Abdullah , Murman Daniel L. , Bashford Gregory R. 
Published: March 2018

ABSTRACTBACKGROUND AND PURPOSECerebrovascular reactivity (CR) is an ideal biomarker to detect cerebrovascular damage. CR can be quantified by measuring changes in cerebral blood flow velocity (CBFV) resulting from a CO2 vasodilatory stimulus, often using the breath‐holding index (BHI). In this method, transcranial Doppler (TCD) ultrasound is used to measure CBFV changes in the middle cerebral artery (MCA) during a breath‐hold maneuver. Despite its convenience, BHI has high variability. Changing body position may contribute to potential variability. It is important to determine if CR differs with body position. The aims of this study were, first, to propose an alternative, more robust index to evaluate CR using a breath‐hold maneuver; second, investigate the effect of body position on CR measured with conventional (BHI) and a new proposed index.METHODSTen healthy young volunteers held their breath for 30 seconds on a tilt table. CR was calculated at five different angles using two indices: the conventional BHI, and the breath‐hold acceleration index (BHAI), a new index obtained by linear regression of the most linear portion of the mean velocity change during the breath‐hold maneuver. The regression represents acceleration (change in blood flow velocity per unit of time) sampled at each cardiac cycle.RESULTSThe mean coefficient of variation was 43.7% lower in BHAI in comparison with BHI. Neither index was statistically significant between body positions (P > .05).CONCLUSIONSBHAI has less variability in comparison with the conventional standard BHI. Additionally, neither index showed statistical significance in CR based on change in body position.
Dental implications in Hajdu–Cheney syndrome: A novel case report and review of the literature
Authors: Lee JW , Kim YJ , Kang J , Shin TJ , Hyun H‐K , Kim Y‐J , Lee S‐H , Lee ZH , Kim J‐W 
Published: March 2018

ObjectiveTo identify the molecular genetic etiology of an individual with a dysmorphic face, unusual teeth mobility, and root resorption.Subjects and MethodsDNA samples were collected from a trio of family members, and whole‐exome sequencing was performed.ResultsMutational analysis revealed a de novo mutation (c.6787C>T) in the last exon of the NOTCH2 gene. This mutation would introduce a premature stop codon [p.(Gln2263*)] and generate a truncated protein without C‐terminus, escaping from the nonsense‐mediated decay system. Sanger sequencing confirmed that this mutation was generated spontaneously.ConclusionsIn this study, we identified a novel nonsense mutation in the last exon of the NOTCH2 gene causing Hajdu–Cheney syndrome. We described the genotype and phenotype correlation and the related dental complications. These results will advance the understanding of the NOTCH2 signaling in periodontitis and root resorption.
The bZip transcription factor HY5 mediates CRY1a‐induced anthocyanin biosynthesis in tomato
Authors: Liu Chao‐Chao , Chi Cheng , Jin Li‐Juan , Zhu Jianhua , Yu Jing‐Quan , Zhou Yan‐Hong 
Published: March 2018

AbstractThe production of anthocyanin is regulated by light and corresponding photoreceptors. In this study, we found that exposure to blue light and overexpression of CRY1a are associated with increased accumulation of anthocyanin in tomato (Solanum lycopersicum L.). These responses are the result of changes in mRNA and the protein levels of SlHY5, which is a transcription factor. In vitro and in vivo experiments using electrophoretic mobility shift assay and ChIP‐qPCR assays revealed that SlHY5 could directly recognize and bind to the G‐box and ACGT‐containing element in the promoters of anthocyanin biosynthesis genes, such as chalcone synthase 1, chalcone synthase 2, and dihydroflavonol 4‐reductase. Silencing of SlHY5 in OE‐CRY1a lines decreased the accumulation of anthocyanin. The findings presented here not only deepened our understanding of how light controls anthocyanin biosynthesis and associated photoprotection in tomato leaves, but also allowed us to explore potential targets for improving pigment production.
Effects of montmorency tart cherry (L. Prunus Cerasus) consumption on nitric oxide biomarkers and exercise performance
Authors: Keane K. M. , Bailey S. J. , Vanhatalo A. , Jones A. M. , Howatson G. 
Published: March 2018

The purpose of this study was to investigate the effects of Montmorency tart cherry juice (MC) on nitric oxide (NO) biomarkers, vascular function, and exercise performance. In a randomized, double‐blind, placebo (PLA)‐controlled, crossover study, 10 trained cyclists (mean ± SD; O2peak 59.0 ± 7.0 mL/kg/min) acutely ingested 30 mL of either MC or PLA following dietary restrictions of polyphenol‐rich compounds and completed 6‐minutes moderate‐ and severe‐intensity cycling bouts 1.5 hour post‐ingestion on 2 occasions for each experimental condition. The severe‐intensity cycling test was continued to exhaustion on 1 occasion and immediately followed by a 60‐seconds all‐out sprint on the other occasion. Blood pressure, pulse wave measures, tissue oxygenation index, and plasma nitrite concentration were assessed pre‐ and 1.5 hour post‐ingestion. Time to exhaustion was not different between conditions (P > .05), but peak power over the first 20 seconds (363 ± 42 vs 330 ± 26 W) and total work completed during the 60‐seconds all‐out sprint (21 ± 3 vs 19 ± 3 kJ) were 10% higher in the MC trial compared to the PLA trial (P < .05). Systolic blood pressure was 5 ± 2 mm Hg lower 1.5 hour post‐MC supplementation compared to PLA supplementation (P < .05). There were no differences in pulse wave measures, plasma nitrite concentration, or tissue oxygenation between the MC and PLA trials (P > .05). These results suggest that acute supplementation with MC can lower blood pressure and improve some aspects of exercise performance, specifically end‐sprint performance, in trained cyclists.
Unbalanced nutrient ratios in pelleted compound recycling fertilizers
Authors: Brod E. , Toven K. , Haraldsen T. K. , Krogstad T. 
Published: March 2018

AbstractThe aim of this study was to contribute to the development of pelleted compound recycling fertilizers with favourable handling and spreading characteristics and balanced nutrient ratios by combining nitrogen (N)‐ and phosphorus (P)‐rich waste resources (meat bone meal, fish sludge or food waste) with potassium (K)‐rich bottom wood ash. Pelleted compound recycling fertilizers with good durability and low dusting tendency were produced by roll‐pelleting preheated waste resources at a suitable moisture content. However, the nutrient ratios in the final products were insufficiently balanced, with too low N concentrations relative to P and K to meet crop demands. In a bioassay using barley (Hordeum vulgare) and a nutrient‐deficient sand/peat mixture, the relative agronomic effectiveness (RAE) of pelleted compound recycling fertilizers and reference recycling fertilizers was 22–42% of that of mineral compound fertilizer. Growth limitation was due to reduced N availability (mineral fertilizer equivalent ‐ MFE = 35–57%) or reduced P availability (MFE = 20–115%), with the greatest P fertilizer value obtained for digestate based on dairy manure and fish sludge. Availability of K in bottom wood ash was masked by the experimental soil.
Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries
Authors: Cáceres Diego H. , Samayoa Blanca E. , Medina Narda G. , Tobón Angela M. , Guzmán Brenda J. , Mercado Danicela , Restrepo Angela , Chiller Tom , Arathoon Eduardo E. , Gómez Beatriz L. 
Published: March 2018

ABSTRACT

Histoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detect
Histoplasma capsulatum
infection in regions where histoplasmosis is endemic would dramatically decrease the time to diagnosis and treatment, reducing morbidity and mortality. The aim of this study was to validate a commercial monoclonal
Histoplasma
galactomannan (HGM) enzyme-linked immunosorbent assay (Immuno-Mycologics [IMMY], Norman, OK, USA) in two cohorts of people living with HIV/AIDS (PLHIV). We analyzed urine samples from 589 people (466 from Guatemala and 123 from Colombia), including 546 from PLHIV and 43 from non-PLHIV controls. Sixty-three of these people (35 from Guatemala and 28 from Colombia) had confirmed histoplasmosis by isolation of
H. capsulatum
. Using the standard curve provided by the quantitative commercial test, the sensitivity was 98% (95% confidence interval [CI], 95 to 100%) and the specificity was 97% (95% CI, 96 to 99%) (cutoff = 0.5 ng/ml). Semiquantitative results, using a calibrator of 12.5 ng/ml of
Histoplasma
galactomannan to calculate an enzyme immunoassay index value (EIV) for the samples, showed a sensitivity of 95% (95% CI, 89 to 100%) and a specificity of 98% (95% CI, 96 to 99%) (cutoff ≥ 2.6 EIV). This relatively simple-to-perform commercial antigenuria test showed a high performance with reproducible results in both countries, suggesting that it can be used to detect progressive disseminated histoplasmosis in PLHIV in a wide range of clinical laboratories in countries where histoplasmosis is endemic.
Intracellular Hepatitis C Virus Modeling Predicts Infection Dynamics and Viral Protein Mechanisms
Authors: Aunins Thomas R. , Marsh Katherine A. , Subramanya Gitanjali , Uprichard Susan L. , Perelson Alan S. , Chatterjee Anushree 
Published: March 2018

ABSTRACT

Hepatitis C virus (HCV) infection is a global health problem, with nearly 2 million new infections occurring every year and up to 85% of these infections becoming chronic infections that pose serious long-term health risks. To effectively reduce the prevalence of HCV infection and associated diseases, it is important to understand the intracellular dynamics of the viral life cycle. Here, we present a detailed mathematical model that represents the full hepatitis C virus life cycle. It is the first full HCV model to be fit to acute intracellular infection data and the first to explore the functions of distinct viral proteins, probing multiple hypotheses of
cis
- and
trans
-acting mechanisms to provide insights for drug targeting. Model parameters were derived from the literature, experiments, and fitting to experimental intracellular viral RNA, extracellular viral titer, and HCV core and NS3 protein kinetic data from viral inoculation to steady state. Our model predicts higher rates for protein translation and polyprotein cleavage than previous replicon models and demonstrates that the processes of translation and synthesis of viral RNA have the most influence on the levels of the species we tracked in experiments. Overall, our experimental data and the resulting mathematical infection model reveal information about the regulation of core protein during infection, produce specific insights into the roles of the viral core, NS5A, and NS5B proteins, and demonstrate the sensitivities of viral proteins and RNA to distinct reactions within the life cycle.

IMPORTANCE
We have designed a model for the full life cycle of hepatitis C virus. Past efforts have largely focused on modeling hepatitis C virus replicon systems, in which transfected subgenomic HCV RNA maintains autonomous replication in the absence of virion production or spread. We started with the general structure of these previous replicon models and expanded it to create a model that incorporates the full virus life cycle as well as additional intracellular mechanistic detail. We compared several different hypotheses that have been proposed for different parts of the life cycle and applied the corresponding model variations to infection data to determine which hypotheses are most consistent with the empirical kinetic data. Because the infection data we have collected for this study are a more physiologically relevant representation of a viral life cycle than data obtained from a replicon system, our model can make more accurate predictions about clinical hepatitis C virus infections.
Paediatric Ebstein’s anomaly: how clinical presentation predicts mortality
Authors: Geerdink Lianne M , Delhaas Tammo , Helbing Willem A , du Marchie Sarvaas Gideon J , Heide Henriette ter , Rozendaal Lieke , de Korte Chris L , Peer Petronella G M , Kuipers Irene M , Kapusta Livia 
Published: March 2018

BackgroundForecasting the prognosis of a child when diagnosed with Ebstein’s anomaly is difficult. We, therefore, studied which factors at the time of diagnosis are associated with death during childhood.MethodsAll consecutive patients (0–18 years) diagnosed with Ebstein’s anomaly in the Netherlands between 1980 and 2014 were included. Survival curves were obtained using the Kaplan-Meier method. By using the Cox proportional hazard model, we analysed the factors (at diagnosis) that were associated with death.ResultsWe included 176 patients. Thirty-one patients (18%) died before the age of 18 years. The 1-year survival was 84% and remained stable at 82% from 35 months after diagnosis and onwards. Modified Ross Heart Failure Class 4 at the time of diagnosis was the most important risk factor for death during childhood (HR 12.5, 95% CI 4.4 to 35.9). Furthermore, diagnosis in the neonatal period (HR 4.2, 95% CI 1.5 to 12.0), severe tricuspid valve regurgitation (HR 2.4, 95% CI 1.2 to 5.0), severe right ventricular outflow tract obstruction (HR 3.7, 95% CI 1.8 to 7.7) and a patent ductus arteriosus (HR 2.8, 95% CI 1.3 to 6.0) at the time of diagnosis were univariately associated with death. Multivariable analysis showed that presentation with Heart Failure Class 4 and a ventricular septal defect is the strongest predictor of death in childhood and adolescence.ConclusionPatients with Ebstein’s anomaly presenting with Heart Failure Class 4 and a ventricular septal defect have a high risk of death during childhood.
Prevalence of the optic disc anomalies in the adult South Indian population
Authors: Bassi Shikha Talwar , George Ronnie , Sen Swarnali , Asokan Rashima , Lingam Vijaya 
Published: March 2018

PurposeTo determine the prevalence of congenitally abnormal disc (all anomalies) in an adult population in southern India.MethodsSubjects aged ≥40 years (n=6013) underwent a complete ophthalmic examination. Optic disc anomalies were diagnosed according to the definitions given in the article.ResultsOptic disc anomalies were found in 81 eyes of 66 (1.1%, 95% CIs 0.00834 to 0.01361) patients. The prevalence of each anomaly in the descending order was peripapillary myelinated nerve fibre (0.28%), epipapillary glial tissue on the optic disc (0.28%), peripapillary vascular loops (0.16%), tilted disc (0.09%), optic disc coloboma (0.08%), optic nerve hypoplasia (0.04%), optic disc pit (0.04%), optic disc pigmentation (0.03%), optic nerve head drusen (0.03%), Bergmeister’s papilla (0.03%), optic disc pit and coloboma (0.01%).ConclusionsThe prevalence of optic disc anomalies is 1.1% in the adult South Indian population.
Levels of detection of hypertension in primary medical care and interventions to improve detection: a systematic review of the evidence since 2000
Authors: Baker Richard , Wilson Andrew , Nockels Keith , Agarwal Shona , Modi Priya , Bankart John 
Published: March 2018

ObjectivesIn England, many hypertensives are not detected by primary medical care. Higher detection is associated with lower premature mortality. We aimed to summarise recent evidence on detection and interventions to improve detection in order to inform policies to improve care.DesignData sources: systematic review of articles published since 2000. Searches of Medline and Embase were undertaken. Eligibility criteria: published in English, any study design, the setting was general practice and studies included patients aged 18 or over. Exclusion criteria: screening schemes, studies in primary care settings other than general practice, discussion or comment pieces. Participants: adult patients of primary medical care services. Synthesis: study heterogeneity precluded a statistical synthesis, and papers were described in summary tables.ResultsSeventeen quantitative and one qualitative studies were included. Detection rates varied by gender and ethnic group, but longitudinal studies indicated an improvement in detection over time. Patient socioeconomic factors did not influence detection, but living alone was associated with lower detection. Few health system factors were associated with detection, but in two studies higher numbers of general practitioners per 1000 population were associated with higher detection. Three studies investigated interventions to improve detection, but none showed evidence of effectiveness.LimitationsThe search was limited to studies published from 2000, in English. There were few studies of interventions to improve detection, and a meta-analysis was not possible.Conclusions and implicationsLevels of detection of hypertension by general practices may be improving, but large numbers of people with hypertension remain undetected. Improvement in detection is therefore required, but guidance for primary medical care is not provided by the few studies of interventions included in this review. Primary care teams should continue to use low-cost, practical approaches to detecting hypertension until evidence from new studies of interventions to improve detection is available.
Mycoplasma genitalium: high prevalence of resistance to macrolides and frequent anorectal infection in men who have sex with men in western Sydney
Authors: Couldwell Deborah L , Jalocon Dean , Power Melissa , Jeoffreys Neisha J , Chen Sharon C-A , Lewis David A 
Published: March 2018

ObjectivesWe aimed to estimate the prevalence of Mycoplasma genitalium infection and of mutations linked to macrolide resistance using the ResistancePlus MG assay (SpeeDx, Sydney, New South Wales, Australia) in first-void urine (FVU), anorectal and oropharyngeal samples from men who have sex with men (MSM) attending Western Sydney Sexual Health Centre (WSSHC).MethodsConsecutive symptomatic and asymptomatic MSM attending for STI testing were prospectively enrolled. M. genitalium testing using the ResistancePlus MG assay was performed on FVU, anorectal and oropharyngeal samples routinely collected for Chlamydia trachomatis and Neisseria gonorrhoeae assays.ResultsOverall, the prevalence of M. genitalium infection in the study group was 13.4% (68/508). Most (79.4%, 54/68) M. genitalium harboured macrolide resistance mutations (87.5% of urethral and 75.6% of anorectal infections). The anorectum was the most commonly infected site (45/505, 8.9%), followed by the urethra (24/508, 4.7%). No oropharyngeal M. genitalium infections were detected (0/508). Most of the anorectal (93.3%) and urethral (79.2%) infections were asymptomatic.MSM who were taking HIV pre-exposure prophylaxis (PrEP) were twice as likely to be infected with M. genitalium compared with MSM who were not on PrEP (OR 2.1, 95% CI 1.3 to 3.6; P=0.0041). Always using condoms for anal sex in the last 3 months was protective of infection (OR 0.8, 95% CI 0.6 to 1.0; P=0.0186).ConclusionsWe demonstrated a high prevalence of M. genitalium and very high levels of macrolide resistance among MSM attending WSSHC. Our findings support the routine use of an assay to detect macrolide resistance mutations in M. genitalium infections. This will ensure, in regions or populations with high rates of macrolide resistance among M. genitalium strains, that first-line treatment with azithromycin will only be used if a macrolide-sensitive strain is identified.