bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct roles of srGAP3‐Rac1 in the initiation and maintenance phases of neuropathic pain induced by paclitaxel
Authors: Chen Zihang , Zhang Subo , Nie Bilin , Huang Jingxiu , Han Zhixiao , Chen Xiaodi , Bai Xiaohui , Ouyang Handong 
Published: April 2020

Key points
Spinal cord dorsal horn srGAP3 (slit‐robo GTPase activating protein 3) increases in the initiation phase of neuropathic pain and decreases in the maintenance phase. However, Rac1 activity, which can be reduced by srGAP3, decreases in the initiation phase and increases in the maintenance phase.
The increased srGAP3 in the initiation phase promotes new immature dendritic spines instigating neuropathic pain. Decreased srGAP3 in the maintenance phase enhances Rac1 activity facilitating maturation of dendritic spines and the persistence of neuropathic pain.
SrGAP3 small interfering RNA can ameliorate neuropathic pain only when administrated in the initiation phase. The Rac1 inhibitor can ameliorate neuropathic pain only when administrated in the maintenance phase.
Combined targeting of srGAP3 in the initiation phase and Rac1 in the maintenance phase can produce optimal analgesic efficacy.
AbstractNeuropathic pain includes an initiation phase and maintenance phase, each with different pathophysiological processes. Understanding the synaptic plasticity and molecular events in these two phases is relevant to exploring precise treatment strategies for neuropathic pain. In the present study, we show that dendritic spine density increases in the spinal dorsal horn in the initiation phase of neuropathic pain induced by paclitaxel and that the spine maturity ratio increases in the maintenance phase. Increased srGAP3 (slit‐robo GTPase activating protein 3) facilitates dendritic spine sprouting in the initiation phase. In the maintenance phase, srGAP3 decreases to upregulate Rac1 activity, which facilitates actin polymerization and dendritic spine maturation and thus the persistence of neuropathic pain. Knockdown of srGAP3 in the initiation phase or inhibition of Rac1 in the maintenance phase attenuates neuropathic pain. Combined intervention of srGAP3 in the initiation phase, and Rac1 in the maintenance phase shows better analgesic efficacy against neuropathic pain. The present study demonstrates the role of srGAP3‐Rac1 in dendritic spine plasticity in the two phases of neuropathic pain and, accordingly, provides treatment strategies for different phases of neuropathic pain.
Estimation of $$\varUpsilon \hbox {(1S)}$$ production in ep process near threshold
Authors: Xu Yu , Xie Yaping , Wang Rong , Chen Xurong 
Published: March 2020

AbstractThe near-threshold photo-productions of heavy quarkonia are important ways to test the QCD-inspired models and to constrain the gluon distribution of nucleon in the large x region. Investigating the various models, we choose a photon–gluon fusion model and a pomeron exchange model for $$\hbox {J}/\varPsi $$J/Ψ photo-production near threshold, emphasising on the explanation of the recent experimental measurement by GlueX at JLab. We find that these two models are not only valid in a wide range of the center-of-mass energy of $$\gamma $$γ and proton, but also can be generalized to describe the $$\varUpsilon \hbox {(1S)}$$Υ(1S) photo-production. Using these two models, we predict the electro-production cross-sections of $$\varUpsilon \hbox {(1S)}$$Υ(1S) at EicC to be 48 fb to 85 fb at the center-of-mass energy of 16.75 GeV.
Environmental Quality and Invasive Breast Cancer
Authors: Gearhart-Serna Larisa M. , Hoffman Kate , Devi Gayathri R. 
Published: April 2020

Abstract
Background: Breast cancer is a complex and multifactorial disease, and environmental factors have been suggested to increase its risk. However, prior research has largely focused on studying exposures to one factor/contaminant at a time, which does not reflect the real-world environment.
Methods: Herein, we investigate associations between breast cancer and the environmental quality index (EQI), a comprehensive assessment of five domains of environmental quality (air, water, land, sociodemographic, and built environments) at the county level. Breast cancer diagnoses for North Carolina women were obtained from the North Carolina Central Cancer Registry (2009–2014) and the county of residence at the time of diagnosis was linked with the EQI. We evaluated the odds of localized, regional, or distant metastatic breast cancer in categories of environmental quality using women with carcinoma in situ as registry-based controls.
Results: Overall environmental quality was generally not associated with invasive breast cancer; however, all breast cancer types tended to be inversely associated with land quality, particularly in more rural communities [distant metastatic breast cancer was 5%–8% more likely (OR, 1.08; 95% confidence interval, 1.02–1.14; P = 0.02) compared with carcinoma in situ].
Conclusions: Cumulatively, our results suggest that some broad measures of environmental quality are associated with invasive breast cancer but that associations vary by environmental domain, cancer stage, subtype, and urbanicity.
Impact: Our findings suggest that components of land quality (e.g., pesticide applications and animal facilities) warrant additional investigation in relation to invasive breast cancer.
See all articles in this CEBP Focus section, “Environmental Carcinogenesis: Pathways to Prevention.”
The Effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition on the Risk of Venous Thromboembolism
Authors: Marston Nicholas A. , Gurmu Yared , Melloni Giorgio E.M. , Bonaca Marc , Gencer Baris , Sever Peter S. , Pedersen Terje R. , Keech Anthony C. , Roselli Carolina , Lubitz Steven A. , Ellinor Patrick T. , O’Donoghue Michelle L. , Giugliano Robert P. , Ruff Christian T. , Sabatine Marc S. 
Published: March 2020

Background:
The relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of VTE, explore potential mechanisms, and examine the efficacy in subgroups with clinically and genetically defined risk.

Methods:
We performed a post hoc analysis of the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) testing whether evolocumab reduces the risk of VTE events (deep venous thrombosis or pulmonary embolism). Data from FOURIER and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) were then combined in a meta-analysis to assess the class effect of PCSK9 inhibition on the risk of VTE. We also analyzed baseline lipids in FOURIER to investigate potential mechanisms explaining the reduction in VTE with evolocumab. Last, an exploratory genetic analysis was performed in FOURIER to determine whether a VTE polygenic risk score could identify high-risk patients who would derive the greatest VTE reduction from evolocumab.

Results:

In FOURIER, the hazard ratio (HR) for VTE with evolocumab was 0.71 (95% CI, 0.50–1.00;
P
=0.05), with no effect in the 1st year (HR, 0.96 [95% CI, 0.57–1.62]) but a 46% reduction (HR, 0.54 [95% CI, 0.33–0.88];
P
=0.014) beyond 1 year. A meta-analysis of FOURIER and ODYSSEY OUTCOMES demonstrated a 31% relative risk reduction in VTE with PCSK9 inhibition (HR, 0.69 [95% CI, 0.53–0.90];
P
=0.007). There was no relation between baseline low-density lipoprotein cholesterol levels and magnitude of VTE risk reduction. In contrast, in patients with higher baseline lipoprotein(a) (Lp[a]) levels, evolocumab reduced Lp(a) by 33 nmol/L and risk of VTE by 48% (HR, 0.52 [95% CI, 0.30–0.89];
P
=0.017), whereas, in patients with lower baseline Lp(a) levels, evolocumab reduced Lp(a) by only 7 nmol/L and had no effect on VTE risk (
P
interaction
0.087 for HR;
P
heterogeneity
0.037 for absolute risk reduction). Modeled as a continuous variable, there was a significant interaction between baseline Lp(a) concentration and magnitude of VTE risk reduction (
P
interaction
=0.04). A polygenic risk score identified patients who were at >2-fold increased risk for VTE and who derived greater relative (
P
interaction
=0.04) and absolute VTE reduction (
P
heterogeneity
=0.009) in comparison with those without high genetic risk.

Conclusions:
PCSK9 inhibition significantly reduces the risk of VTE. Lp(a) reduction may be an important mediator of this effect, a finding of particular interest given the ongoing development of potent Lp(a) inhibitors.
Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome
Authors: Schwartz Gregory G. , Steg Philippe Gabriel , Szarek Michael , Bittner Vera A. , Diaz Rafael , Goodman Shaun G. , Kim Yong-Un , Jukema J. Wouter , Pordy Robert , Roe Matthew T. , White Harvey D. , Bhatt Deepak L. ,   For the ODYSSEY OUTCOMES Committees and Investigators*
Published: March 2020

Background:
Patients with acute coronary syndrome are at risk for peripheral artery disease (PAD) events and venous thromboembolism (VTE). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors reduce lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C) levels. Our objective was to ascertain whether PCSK9 inhibition reduces the risk of PAD events or VTE after acute coronary syndrome, and if such effects are related to levels of lipoprotein(a) or LDL-C.

Methods:

This was a prespecified analysis of the ODYSSEY OUTCOMES randomized clinical trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome), which was conducted in 18 924 patients with recent acute coronary syndrome on intensive or maximum-tolerated statin treatment who were randomized to the PCSK9 inhibitor alirocumab or placebo. In a prespecified analysis, PAD events (critical limb ischemia, limb revascularization, or amputation for ischemia) and VTE (deep vein thrombosis or pulmonary embolism) were assessed. LDL-C was corrected (LDL-C
corrected
) for cholesterol content in lipoprotein(a).

Results:

At baseline, median lipoprotein(a) and LDL-C
corrected
were 21 and 75 mg/dL, respectively; with alirocumab, median relative reductions were 23.5% and 70.6%, respectively. PAD events and VTE occurred in 246 and 92 patients, respectively. In the placebo group, risk of PAD events was related to baseline quartile of lipoprotein(a) (
P
trend
=0.0021), and tended to associate with baseline quartile of LDL-C
corrected
(
P
trend
=0.06); VTE tended to associate with baseline quartile of lipoprotein(a) (
P
trend
=0.06), but not LDL-C
corrected
(
P
trend
=0.85). Alirocumab reduced risk of PAD events (hazard ratio [HR], 0.69 [95% CI, 0.54–0.89];
P
=0.004), with nonsignificantly fewer VTE events (HR, 0.67 [95% CI, 0.44–1.01];
P
=0.06). Reduction in PAD events with alirocumab was associated with baseline quartile of lipoprotein(a) (
P
trend
=0.03), but not LDL-C
corrected
(
P
trend
=0.50). With alirocumab, the change from baseline to Month 4 in lipoprotein(a), but not LDL-C
corrected
, was associated with the risk of VTE and the composite of VTE and PAD events.

Conclusions:
In statin-treated patients with recent acute coronary syndrome, risk of PAD events is related to lipoprotein(a) level and is reduced by alirocumab, particularly among those with high lipoprotein(a). Further study is required to confirm whether risk of VTE is related to lipoprotein(a) level and its reduction with alirocumab.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01663402.
Risk/Benefit Tradeoff of Antithrombotic Therapy in Patients With Atrial Fibrillation Early and Late After an Acute Coronary Syndrome or Percutaneous Coronary Intervention
Authors: Alexander John H. , Wojdyla Daniel , Vora Amit N. , Thomas Laine , Granger Christopher B. , Goodman Shaun G. , Aronson Ronald , Windecker Stephan , Mehran Roxana , Lopes Renato D. 
Published: March 2020

Background:
In AUGUSTUS (Open-Label, 2×2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention), patients with atrial fibrillation and a recent acute coronary syndrome and those undergoing percutaneous coronary intervention had less bleeding with apixaban than vitamin K antagonist (VKA) and with placebo than aspirin. However, the number of ischemic events was numerically higher with placebo. The aim of this analysis is to assess the tradeoff of risk (bleeding) and benefit (ischemic events) over time with apixaban versus VKA and aspirin versus placebo.

Methods:

In AUGUSTUS, 4614 patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention on a P2Y
12
inhibitor were randomized to blinded aspirin or placebo and to open-label apixaban or VKA for 6 months. In a post hoc analysis, we compared the risk of 3 composite bleeding outcomes and 3 composite ischemic outcomes from randomization through 30 days and from 30 days to 6 months with apixaban and VKA and with aspirin and placebo.

Results:
Compared with VKA, apixaban had either a lower or a similar risk of bleeding and ischemic outcomes from randomization to 30 days and from 30 days to 6 months. From randomization to 30 days, aspirin caused more severe bleeding (absolute risk difference, 0.97% [95% CI, 0.23–1.70]) and fewer severe ischemic events (absolute risk difference, −0.91% [95% CI, −1.74 to −0.08]) than placebo. From 30 days to 6 months, the risk of severe bleeding was higher with aspirin than placebo (absolute risk difference, 1.25% [95% CI, 0.23–2.27]), whereas the risk of severe ischemic events was similar (absolute risk difference, −0.17% [95% CI, −1.33 to 0.98]).

Conclusions:

In patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention receiving a P2Y
12
inhibitor, apixaban is preferred over VKA. Use of aspirin immediately and for up to 30 days results in an equal tradeoff between an increase in severe bleeding and a reduction in severe ischemic events. After 30 days, aspirin continues to increase bleeding without significantly reducing ischemic events. These results inform shared, patient-centric decision making on the ideal duration of the use of aspirin after an acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation receiving oral anticoagulation.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02415400.
Full-Spectrum Analysis of Perovskite-Based Surface Plasmon Nanolasers
Authors: Cheng Pi-Ju , Zheng Qi-Yan , Hsu Chu-Yuan , Li Heng , Hong Kuo-Bin , Zhu Yizhi , Cui Qiannan , Xu Chunxiang , Lu Tien-Chang , Lin Tzy-Rong 
Published: March 2020

AbstractWe systematically studied the characteristics of hybrid perovskite-based surface plasmon nanolasers. If one changes the anion composition of perovskites, the emission wavelength can be easily tuned. We conducted in full-spectrum modeling that featured hybrid perovskite nanowires placed on different SiO2-coated metallic (Au, Ag, and Al) plates. The proposed nanocavities that supported plasmonic gap modes exhibited distinguished properties of nanolasers, such as low-transparency threshold-gain and low lasing threshold. The corresponding experimental results for the MAPbBr3 nanolaser on Ag revealed the low-threshold operation. These superior features were attributed to enhanced light-matter interaction with strong coupling. Therefore, the proposed scheme, integrated with hybrid perovskite as gain material, provides an excellent platform for nanoscale plasmon lasing in the visible to near-infrared spectra.
The modified functional comorbidity index performed better than the Charlson index and original functional comorbidity index in predicting functional outcome in geriatric rehabilitation: a prospective observational study
Authors: Kabboord Anouk D. , Godfrey Deborah , Gordon Adam L. , Gladman John R. F. , Van Eijk Monica , van Balen Romke , Achterberg Wilco P. 
Published: March 2020

Abstract
Background
In the inpatient rehabilitation of older patients, estimating to what extent the patient may functionally recover (functional prognosis), is important to plan the rehabilitation programme and aid discharge planning. Comorbidity is very common in older patients. However, the role of comorbidity in making a functional prognosis is not clearly defined. The aim of this study was to investigate a modified and weighted Functional Comorbidity Index (w-FCI) in relation to functional recovery and compare its predictive performance with that of the Charlson comorbidity index (CCI) and the original Functional Comorbidity Index (FCI).

Methods
The COOPERATION study (Comorbidity and Outcomes of Older Patients Evaluated in RehabilitATION) is a prospective observational cohort study. Data of patients that were admitted in an inpatient geriatric rehabilitation facility in the UK between January and September 2017, were collected. The outcome measures were: the Elderly Mobility Scale (EMS) and Barthel index (BI) at discharge, EMS gain/day and BI gain/day. Baseline comorbidity was assessed using the CCI, the FCI and the w-FCI. Correlations, receiver operating curves (ROC), and multiple linear regression analyses were performed. The models were adjusted for age, gender and EMS or BI on admission.

Results
In total, 98 patients (mean age 82 years; 37% male) were included. The areas under the ROC curves of the w-FCI (EMS at discharge: 0.72, EMS gain/day: 0.72, BI at discharge: 0.66 and BI gain/day: 0.60) were higher than for the CCI (0.50, 0.53, 0.49, 0.44 respectively) and FCI (0.65, 0.55, 0.60, 0.49 respectively). The w-FCI was independently associated with EMS at discharge (20.7% of variance explained (PVE), p < 0.001), EMS gain/day (11.2PVE, p < 0.001), and BI at discharge (18.3 PVE, p < 0.001). The FCI was only associated with EMS gain/day (3.9 PVE, p < 0.05). None of the comorbidity indices contributed significantly to BI gain/day (w-FCI: 2.4 PVE, p > 0.05).

Conclusions
The w-FCI was predictive of mobility & function at discharge and mobility gain per day, and outperformed the original FCI and the CCI. The w-FCI could be useful in assessing comorbidity in a personalised way and aid functional prognosis at the start of rehabilitation.
Effect of age at vaccination on the measles vaccine effectiveness and immunogenicity: systematic review and meta-analysis
Authors: Carazo Sara , Billard Marie-Noëlle , Boutin Amélie , De Serres Gaston 
Published: March 2020

AbstractBackgroundThe objectives of this review were to evaluate the effect of age at administration of the first dose of a measles-containing vaccine (MCV1) on protection against measles and on antibody response after one- and two-dose measles vaccinations.MethodsWe conducted a systematic review of the PubMed/MEDLINE, Embase, Web of Science and Cochrane databases (1964–2017) to identify observational studies estimating vaccine effectiveness and/or measles attack rates by age at first vaccination as well as experimental studies comparing seroconversion by age at first vaccination. Random effect models were used to pool measles risk ratios (RR), measles odds ratios (OR) and seroconversion RR of MCV1 administered at < 9, 9–11 or ≥ 15 months compared with 12 or 12–14 months of age.ResultsWe included 41 and 67 studies in the measles protection and immunogenicity analyses. Older age at MCV1, from 6 to ≥15 months, improved antibody response and measles protection among one-dose recipients. Pooled measles RR ranged from 3.56 (95%CI: 1.28, 9.88) for MCV1 at < 9 months to 0.48 (95%CI: 0.36, 0.63) for MCV1 at ≥15 months, both compared to 12–14 months. Pooled seroconversion RR ranged from 0.93 (95%CI: 0.90, 0.96) for MCV1 at 9–11 months to 1.03 (95%CI: 1.00, 1.06) for MCV1 at ≥15 months, both compared to 12 months. After a second dose, serological studies reported high seropositivity regardless of age at administration of MCV1 while epidemiological data based on few studies suggested lower protection with earlier age at MCV1.ConclusionsEarlier age at MCV1 decreases measles protection and immunogenicity after one dose and might still have an impact on vaccine failures after two doses of measles vaccine. While two-dose vaccination coverage is most critical to interrupt measles transmission, older age at first vaccination may be necessary to keep the high level of population immunity needed to maintain it.
Quality, availability and storage conditions of oxytocin and misoprostol in Malawi
Authors: Hagen Nhomsai , Khuluza Felix , Heide Lutz 
Published: March 2020

Abstract
Background
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low- and middle-income countries (LMICs). Oxytocin and misoprostol are used for the prevention and treatment of PPH. However, both medicines are chemically unstable and sensitive to environmental conditions. Previous studies reported a high prevalence of substandard oxytocin and misoprostol preparations in LMICs.

Methods
In randomly selected health facilities of four districts of Malawi, the availability of oxytocin and misoprostol was determined, and the knowledge of health workers on storage requirements and use of oxytocics was assessed. Temperature loggers were used to record the storage temperature of oxytocics. Samples of oxytocin injections and misoprostol tablets were collected from the health facilities and from wholesalers. Oxytocin samples were analysed for identity, assay (= quantity of oxytocin) and for pH value according to United States Pharmacopeia 40. Misoprostol samples were analysed for identity, assay, dissolution and related substances according to the International Pharmacopeia 2017.

Results
All visited hospitals and health centers had oxytocin available. At non-refrigerated storage sites, the recorded mean kinetic temperature exceeded the oxytocic’s storage temperature stated on the labels in 42% of the sites. At refrigerated storage sites, the required temperature of 2–8 °C was exceeded in 33% of the sites. Out of 65 oxytocin samples, 7 (11%) showed moderate deviations from specification, containing 82.2–86.8% of the declared amount of oxytocin. Out of 30 misoprostol samples, 5 (17%) showed extreme deviations, containing only 12.7–30.2% of the declared amount. The extremely substandard misoprostol was reported to the national authorities and to WHO, leading to an immediate recall of the respective brand in Malawi. The UK-based distributor of this brand closed its business shortly thereafter.

Conclusion
Availability of oxytocin was excellent in Malawi, and its quality was better than reported in previous studies in other LMICs. However, storage conditions at the health facilities often did not meet the requirements. Extremely substandard misoprostol tablets were found, representing a serious risk to maternal health. This shows the need for continued efforts for quality assurance in medicine procurement and registration, as well as for post-marketing surveillance.