bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefits of adding a physician-staffed ambulance to bystander-witnessed out-of-hospital cardiac arrest: a community-based, observational study in Niigata, Japan
Authors: Sato Nobuhiro , Matsuyama Tasuku , Akazawa Kohei , Nakazawa Kyoko , Hirose Yasuo 
Published: November 2019

ObjectiveThis study aimed to assess the benefits of adding a physician-staffed ambulance to bystander-witnessed out-of-hospital cardiac arrest using a community-based registry.DesignPopulation-based, retrospective cohort study.SettingAn urban city with approximately 800 000 residents.ParticipantsPatients aged ≥18 years with bystander-witnessed out-of-hospital cardiac arrests of medical aetiology in Niigata City, Japan, between January 2012 and December 2016, according to the Utstein style.Primary and secondary outcome measuresThe primary outcome was 1-month survival with a favourable neurological outcome, defined as a cerebral performance category score of 1 or 2. We used logistic regression analysis to assess the association between favourable neurological outcome and prehospital physician involvement.ResultsDuring the study period, a total of 4172 cardiac arrests were registered; of these, 892 patients with out-of-hospital cardiac arrest were eligible for this analysis, among whom 135 (15.1%) had prehospital physician involvement and 757 (84.9%) did not have prehospital physician involvement. The percentage of favourable neurological outcomes was 20.7% (28 of 135) in those with physician involvement and 10.4% (79 of 757) in those without physician involvement (p=0.001). Using multivariable logistic regression, prehospital physician involvement had an OR for a favourable neurological outcome of 3.44 (95% CI 1.64 to 7.23).ConclusionsAmong adults with out-of-hospital cardiac arrest, adding a physician-staffed ambulance was associated with significantly greater favourable neurological outcomes than standard emergency medical services.
Sickle cell disease and thalassaemia antenatal screening programme in England over 10 years: a review from 2007/2008 to 2016/2017
Authors: Weil Leonora G , Charlton Matthew RM , Coppinger Cathy , Daniel Yvonne , Streetly Allison 
Published: November 2019

ObjectivesTo evaluate the antenatal sickle cell and thalassaemia screening programme in England over 10 years from 1 April 2007 to 31 March 2017.MethodsFour routine data sources were used: antenatal screening laboratory data; key performance indicator data from maternity trusts; prenatal diagnosis (PND) laboratory data and data from screening incidents.ResultsFor the 10 years examined a total of 6608 575 booking samples were reported as screened, and 154 196 pregnant women required further testing. There were 3941 reported PND tests of which there were 964 affected fetal results. Antenatal test coverage and Family Origin Questionnaire completion rates are high and increasing; the proportion of tests declined has decreased. However, there is wide variation in the timing of antenatal tests and completeness of follow-up and testing. Since 2014/2015 a lower proportion of PND tests are performed by the programme standard of 12+6 weeks. Results suggest that PND timing affects reproductive choices as those with an affected fetus identified by PND testing earlier are more likely to terminate the pregnancy.ConclusionsThe screening programme appears to be widely accepted as part of routine antenatal care in England. However, the timeliness of screening and subsequent PND testing has consistently not met programme standards. Improving timeliness would enable individuals to consider their options to make informed choices for their pregnancies at the appropriate time. This paper reports carrier rates for an almost complete cohort of women which provides important epidemiological information on the genetic profile of women in England.
Eligibility for late endovascular treatment using DAWN, DEFUSE-3, and more liberal selection criteria in a stroke center
Authors: Nannoni Stefania , Strambo Davide , Sirimarco Gaia , Amiguet Michael , Vanacker Peter , Eskandari Ashraf , Saliou Guillaume , Wintermark Max , Dunet Vincent , Michel Patrik 
Published: November 2019

Background and purposeThe real-life application of DAWN and DEFUSE-3 trials has been poorly investigated. We aimed to identify the proportion of patients with acute ischemic stroke (AIS) eligible for late endovascular treatment (EVT) in our stroke center based on trial and more liberal selection criteria.MethodsAll consecutive patients in our stroke registry (2003–2017) admitted within 5–23 hours of last proof of good health were selected if they had complete clinical and radiological datasets. We calculated the proportion of patients eligible for late EVT according to trial (DAWN and/or DEFUSE-3) and more liberal clinical/imaging mismatch criteria (including lower admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score for core estimation).ResultsOf 1705 patients with AIS admitted to our comprehensive stroke center in the late time window, we identified 925 patients with complete clinical and radiological data. Among them, the proportions of late EVT eligibility were 2.5% (n=23) with DAWN, 5.1% (n=47) with DEFUSE-3, and 11.1% (n=103) with more liberal criteria. Considering late-arriving patients with large vessel occlusion (n=221), the percentages of eligible patients were 10.4%, 21.3%, and 46.6%, respectively. A favorable outcome was observed at comparable rates in treated patients selected by trial or liberal criteria (67% vs 58%, p=0.49).ConclusionsIn a long-term stroke registry, the proportion of late EVT eligibility varied greatly according to selection criteria and referral pattern. Among late-arriving patients referred to our comprehensive stroke center, we found 5.6% eligible according to trial (DAWN/DEFUSE-3) and 11.1% according to liberal criteria. These data indicate that late EVT could be offered to a larger population of patients if more liberal criteria are applied.
Impact of newborn screening on outcomes and social inequalities in cystic fibrosis: a UK CF registry-based study
Authors: Schlüter Daniela K , Southern Kevin W , Dryden Carol , Diggle Peter , Taylor-Robinson David 
Published: November 2019

BackgroundNewborn bloodspot screening (NBS) for cystic fibrosis (CF) was introduced across the UK in 2007 but the impact on clinical outcomes and health inequalities for children with CF is unclear.MethodsWe undertook longitudinal analyses of UK CF registry data on over 3000 children with CF born between 2000 and 2015. Clinical outcomes were the trajectories of percent predicted forced expiratory volume in one second (%FEV1) from age 5, weight for age and body mass index (BMI) SD-scores from age one, and time to chronic Pseudomonas aeruginosa (cPA) infection. Using mixed effects and time-to-event models we assessed the association of NBS with outcomes and potential interactions with childhood socioeconomic conditions, while adjusting for confounders.ResultsNBS was associated with higher average lung function trajectory (+1.56 FEV1 percentage points 95% CI 0.1 to 3.02, n=2216), delayed onset of cPA, and higher average weight trajectory intercept at age one (+0.16 SD; 95% CI 0.07 to 0.26, n=3267) but negative rate of weight change thereafter (−0.02 SD per year; 95% CI −0.03 to −0.00). We found no significant association of NBS with BMI or rate of change of lung function. There was no clear evidence of an impact of NBS on health inequalities early in life.ConclusionsChildren diagnosed with CF by NBS in the UK have better lung function and increased early weight but NBS does not appear to have narrowed early health inequalities.
Toll-like Receptor-6 Signaling Prevents Inflammation and Impacts Composition of the Microbiota During Inflammation-Induced Colorectal Cancer
Authors: Kim Jee-Hyun , Kordahi Melissa C. , Chac Denise , DePaolo R. William 
Published: November 2019

AbstractTightly regulated immune responses must occur in the intestine to avoid unwanted inflammation, which may cause chronic sequela leading to diseases such as colorectal cancer. Toll-like receptors play an important role in preventing aberrant immune responses in the intestine by sensing endogenous commensal microbiota and delivering important regulatory signals to the tissue. However, the role that specific innate receptors may play in the development of chronic inflammation and their impact on the composition of the colonic microbiota is not well understood. Using a model of inflammation-induced colorectal cancer, we found that Lactobacillus species are lost more quickly in wild-type (WT) mice than TLR6-deficient mice resulting in overall differences in bacterial composition. Despite the longer retention of Lactobacillus, the TLR6-deficient mice presented with more tumors and a worse overall outcome. Restoration of the lost Lactobacillus species suppressed inflammation, reduced tumor number, and prevented change in the abundance of Proteobacteria only when given to WT mice, indicating the effect of these Lactobacillus are TLR6 dependent. We found that the TLR6-dependent effects of Lactobacillus could be dissociated from one another via the involvement of IL10, which was necessary to dampen the inflammatory microenvironment, but had no effect on bacterial composition. Altogether, these data suggest that innate immune signals can shape the composition of the microbiota under chronic inflammatory conditions, bias the cytokine milieu of the tissue microenvironment, and influence the response to microbiota-associated therapies.
Effects of 2-Phenethyl Isothiocyanate on Metabolism of 1,3-Butadiene in Smokers
Authors: Boldry Emily J. , Yuan Jian-Min , Carmella Steven G. , Wang Renwei , Tessier Katelyn , Hatsukami Dorothy K. , Hecht Stephen S. , Tretyakova Natalia Y. 
Published: November 2019

Abstract
2-Phenethyl isothiocyanate (PEITC) is a natural product found as a conjugate in cruciferous vegetables. It has been reported to have preventative properties against lung cancer and to inhibit metabolic activation of tobacco carcinogens. In this study, we evaluated the ability of PEITC to influence the metabolism of the human carcinogen 1,3-butadiene in current smokers in a phase II clinical trial with a crossover design. Urinary mercapturic acids of 1,3-butadiene were quantified at baseline and during PEITC treatment. Seventy-nine smokers were randomly assigned to one of two arms: PEITC followed by placebo or placebo followed by PEITC. During the 1-week treatment period, each subject took PEITC (10 mg in 1 mL of olive oil, 4 times per day). There was a 1-week washout period between the PEITC and placebo periods. Oral ingestion of PEITC increased urinary levels of BD-mercapturic acids (MHBMA and DHBMA) by 11.1% and 3.7%, respectively, but these increases were not statistically significant (P = 0.17 and 0.64, respectively). A much stronger effect was observed among subjects with the null genotype of both GSTM1 and GSTT1: in these individuals, PEITC increased urinary levels of MHBMA by 58.7% (P = 0.004) and 90.0% (P = 0.001), respectively, but did not have a significant effect on urinary DHBMA. These results reveal a potentially protective effect of PEITC treatment with respect to the detoxification of 1,3-butadiene in cigarette smokers, specifically in those null for GSTT1, and provide further evidence in support of stronger chemopreventive effects from consumption of dietary isothiocyanates in these individuals.
Plasma Kallikrein Contributes to Coagulation in the Absence of Factor XI by Activating Factor IX
Authors: Visser Mayken , van Oerle René , ten Cate Hugo , Laux Volker , Mackman Nigel , Heitmeier Stefan , Spronk Henri M.H. 
Published: November 2019

Objectives:
FXIa (factor XIa) induces clot formation, and human congenital FXI deficiency protects against venous thromboembolism and stroke. In contrast, the role of FXI in hemostasis is rather small, especially compared with FIX deficiency. Little is known about the cause of the difference in phenotypes associated with FIX deficiency and FXI deficiency. We speculated that activation of FIX via the intrinsic coagulation is not solely dependent on FXI(a; activated FXI) and aimed at identifying an FXI-independent FIX activation pathway.

Approach and Results:

We observed that ellagic acid and long-chain polyphosphates activated the coagulation system in FXI-deficient plasma, as could be demonstrated by measurement of thrombin generation, FIXa-AT (antithrombin), and FXa-AT complex levels, suggesting an FXI bypass route of FIX activation. Addition of a specific PKa (plasma kallikrein) inhibitor to FXI-deficient plasma decreased thrombin generation, prolonged activated partial thromboplastin time, and diminished FIXa-AT and FXa-AT complex formation, indicating that PKa plays a role in the FXI bypass route of FIX activation. In addition, FIXa-AT complex formation was significantly increased in
F11

−/−

mice treated with ellagic acid or long-chain polyphosphates compared with controls and this increase was significantly reduced by inhibition of PKa.

Conclusions:
We demonstrated that activation of FXII leads to thrombin generation via FIX activation by PKa in the absence of FXI. These findings may, in part, explain the different phenotypes associated with FIX and FXI deficiencies.
Persistent Renal Dysfunction in Patients Undergoing Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction
Authors: Kurogi Kazumasa , Ishii Masanobu , Sakamoto Kenji , Komaki Soichi , Marume Kyohei , Kusaka Hiroaki , Yamamoto Nobuyasu , Arima Yuichiro , Yamamoto Eiichiro , Kaikita Koichi , Tsujita Kenichi 
Published: November 2019

Background

The long‐term prognosis of patients with acute myocardial infarction who develop persistent renal dysfunction (
RD
) remains unclear. We investigated risk factors and prognostic implications of persistent
RD
after contrast‐induced nephropathy (
CIN
) in patients with acute myocardial infarction after primary percutaneous coronary intervention.

Methods and Results

We enrolled 952 consecutive patients who underwent primary percutaneous coronary intervention for acute myocardial infarction.
CIN
was defined as an increase in serum creatinine levels ≥0.5 mg/dL or ≥25% from baseline within 72 hours after percutaneous coronary intervention. Persistent
RD
was defined as residual impairment of renal function over 2 weeks, and transient
RD
was defined as recovery of renal function within 2 weeks, after
CIN
. The overall incidence of
CIN
was 8.8% and that of persistent
CIN
was 3.1%. A receiver‐operator characteristic curve showed that the optimal cutoff value of the contrast volume/baseline estimated glomerular filtration rate ratio for persistent
CIN
was 3.45. In multivariable logistic analysis, a contrast volume/baseline estimated glomerular filtration rate >3.45 was an independent correlate of persistent
RD
. At 3 years, the incidence of death was significantly higher in patients with persistent
RD
than in those with transient
RD
(
P
=0.001) and in those without
CIN
(
P
<0.001). Cox regression analysis showed that persistent
RD
(hazard ratio, 4.99; 95% CI, 2.30–10.8;
P
<0.001) was a significant risk factor for mortality. A similar trend was observed for the combined end points, which included mortality, hemodialysis, stroke, and acute myocardial infarction.

Conclusions

Persistent
RD
, but not transient
RD
, is independently associated with long‐term mortality. A contrast volume/baseline estimated glomerular filtration rate >3.45 is an independent predictor of persistent
RD
.
Assimilation of Middepth Velocities from Argo Floats in the Western South China Sea
Authors: Wang Pinqiang , Zhang Weimin , Wang Huizan , Dai Haijin , Wang Xiaohui 
Published: November 2019

AbstractPrevious studies are mainly limited to temperature and salinity (T/S) profiling data assimilation, while data assimilation based on Argo float trajectory information has received less research focus. In this study, a new method was proposed to assimilate Argo trajectory data: the middepth (indicates the parking depth of Argo floats in this study, ~1200 m) velocities are estimated from Argo trajectories and subsequently assimilated into the Regional Ocean Model System (ROMS) using four-dimensional variational data assimilation (4DVAR) method. This method can avoid a complicated float trajectory model in direct position assimilation. The 2-month assimilation experiments in South China Sea (SCS) showed that this proposed method can effectively assimilate Argo trajectory information into the model and improve middepth velocity field by adjusting the unbalanced component in the velocity increments. The assimilation of the Argo trajectory-derived middepth velocity with other observations (satellite observations and T/S profiling data) together yielded the best performance, and the velocity fields at the float parking depth are more consistent with the Argo float trajectories. In addition, this method will not decrease the assimilation performance of other observations [i.e., sea level anomaly (SLA), sea surface temperature (SST), and T/S profiles], which is indicative of compatibility with other observations in the 4DVAR assimilation system.
Pharmacological characterisation of MDI-222, a novel AMPA receptor positive allosteric modulator with an improved safety profile
Authors: Ward Simon E , Harries Mark H , Aldegheri Laura , Bradford Andrea M , Ballini Elisa , Dawson Lee , Lacroix Laurent , Pardoe Joanne , Starr Kathryn , Weil Annette , Waters Kerry , Atack John R , Woolley Marie 
Published: November 2019

Purpose: There is considerable interest in positive allosteric modulators (PAMs) of the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) subtype of ionotropic glutamate receptors as therapeutic agents for a range of cognitive and mood disorders. However, the challenge is to increase AMPA receptor (AMPAR) function sufficient to enhance cognitive function but not to the extent that there are mechanism-related pro-convulsant or convulsant side effects. In this present study, we report the preclinical pharmacology data for MDI-222, an AMPAR PAM which enhances cognition but has a much reduced side-effect (i.e. convulsant) liability relative to other molecules of this mechanism. Methods: The pharmacological effects of MDI-222 were characterised in in vitro and in vivo preclinical electrophysiology, efficacy (cognition), side-effect (pro-convulsant/convulsant), tolerability and toxicity assays. Results: We demonstrate that MDI-222 is an AMPAR PAM, since it enhanced AMPAR function in vitro at human (hGluA1-4) and rat (rGluA2) homomeric receptors, and potentiated hetero-oligomeric AMPARs in rat neurons. MDI-222 enhanced electrically evoked AMPAR-mediated synaptic transmission in the anaesthetised rat at 10 mg/kg (administered intravenously) and did not significantly lower the seizure threshold in the pro-convulsant maximal electroshock threshold test (MEST) at any dose tested up to a maximum of 30 mg/kg (administered by oral gavage (p.o.)). MDI-222 reversed a delay-induced deficit in novel object recognition (NOR) in rats with a minimum effective dose (MED) of 0.3 mg/kg (p.o.) following acute administration, which was reduced to 0.1 mg/kg following sub-chronic administration, and improved passive avoidance performance in scopolamine-impaired rats with a MED of 10 mg/kg p.o. On the other hand, MDI-222 was not pro-convulsant in the MEST, resulting in a therapeutic window between plasma concentrations that enhanced cognitive performance and those associated with mechanism-related side effects of ⩾1000-fold. Unfortunately, despite the excellent preclinical profile of this compound, further development had to be halted due to non-mechanism-related issues. Conclusions: We conclude that MDI-222 is an AMPAR PAM which enhances cognitive performance in rats and has a significantly improved safety profile in preclinical species.
Multidisciplinary Team Utilizing Pharmacists in Multimodal, Bundled Care Reduce Chronic Obstructive Pulmonary Disease Hospital Readmission Rates
Authors: Gentene Anthony J. , Guido Maria Rose , Woolf Brittany , Dalhover Amber , Boesken Timmi Anne , Mueller Eric W. , Zafar Muhammad Ahsan 
Published: November 2019

Background: Chronic obstructive pulmonary disease (COPD) is a major contributor of morbidity and mortality in the United States resulting in high hospitalization and readmission rates. For health systems, identifying an effective strategy to reduce COPD readmissions has remained difficult. Multiple COPD care bundles have been developed with varying degrees of success. Bundles that were multidisciplinary and included pharmacists were successful in reducing readmissions. Objective: To describe and assess a multidisciplinary, 5-element, COPD care bundle that was implemented in an academic, urban safety-net hospital to reduce COPD readmissions and the role of pharmacists in bundle implementation. Methods: A multidisciplinary team collaborated to develop a 5-element COPD care bundle that met unmet patient needs. The bundle elements included the following, with pharmacy responsible for the first two: optimization of COPD inhalers, 30-day supply of insurance-compatible inhalers, individualized patient inhaler teaching, provision of standardized discharge instructions, and scheduling of a 15-day discharge follow-up appointment. Bundle was implemented with multiple Plan-Do-Study-Act (PDSA) cycles to develop intra- and interdepartment processes. Results: Prior to bundle implementation, the health system COPD readmission rates were 22.7%. Reliable implementation of the bundle reduced readmissions to 14.7% over a 6-month period. Pharmacy adherence to completion of the bundle was over 95% over 2 years of bundle use. Conclusion: Pharmacists have a crucial role in hospital-based transitions of care to reduce COPD readmissions.
Targeted Inhibitory Effect of Nasopharyngeal Carcinoma Cells by Hre2.Grp78 Chimeric Promoter Regulating Fusion Gene TK/VP3
Authors: Li Jin-Yun , Huang Wen-Xiao , Chen Jie , Zhao Su-Ping , Tang Yao-Yun 
Published: November 2019

Objective: To construct plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3 and elaborate the effects of overexpressed TK/VP3 on nasopharyngeal carcinoma cells. Methods: Four plasmids were constructed, including pcDNA3.1-CMV-TK/VP3, pcDNA3.1-Hre2.TK/VP3, pcDNA3.1-Grp78.TK/VP3, and pcDNA3.1-Hre2.Grp78.TK/VP3. The human nasopharyngeal carcinoma cell line HNE1 cells were transfected with the 4 plasmids, respectively. Cell viabilities were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was conducted using flow cytometry analysis. The expression of TK, VP3, Grp78, and hypoxia-inducible factor 1α and apoptosis-related proteins was determined by real-time quantitative polymerase chain reaction and Western blotting. Results: The recombinant plasmids that could steadily overexpress TK and VP3 were successfully constructed. Expression of TK and VP3 in cells transfected with pcDNA3.1-Hre2.TK/VP3 and pcDNA3.1-Grp78.TK/VP3 was significantly higher than pcDNA3.1-CMV-TK/VP3, and expression in cells transfected with pcDNA3.1-Hre2.Grp78.TK/VP3 was the highest. Under glucose deprivation or hypoxia condition, Grp78 or hypoxia-inducible factor 1α was overexpressed so that expression of TK and VP3 was significantly upregulated, which could further inhibit cell proliferation and enhance cell apoptosis. Conclusion: We successfully constructed 4 plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3, which could significantly inhibit the proliferation as well as enhance the apoptosis of nasopharyngeal carcinoma cells under glucose deprivation or hypoxia condition.