bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage
Authors: Macdonald R Loch , Hänggi Daniel , Ko Nerissa U , Darsaut Tim E , Carlson Andrew P , Wong George K , Etminan Nima , Mayer Stephan A , Aldrich E Francois , Diringer Michael N , Ng David , Strange Poul , Bleck Thomas , Grubb Robert , Suarez Jose I ,   on behalf of the NEWTON Investigators
Published: September 2020

ABSTRACT

BACKGROUND
A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH).

OBJECTIVE
To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects.

METHODS
Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated.

RESULTS
The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups.

CONCLUSION
Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported.
TERT promoter mutation associated with multifocal phenotype and poor prognosis in patients with IDH wild-type glioblastoma
Authors: Kikuchi Zensho , Shibahara Ichiyo , Yamaki Tetsu , Yoshioka Ema , Shofuda Tomoko , Ohe Rintaro , Matsuda Ken-ichiro , Saito Ryuta , Kanamori Masayuki , Kanemura Yonehiro , Kumabe Toshihiro , Tominaga Teiji , Sonoda Yukihiko 
Published: September 2020

Abstract

Background
Although mutations in the promoter region of the telomerase reverse transcriptase (TERTp) gene are the most common alterations in glioblastoma (GBM), their clinical significance remains unclear. Therefore, we investigated the impact of TERTp status on patient outcome and clinicopathological features in patients with GBM over a long period of follow-up.

Methods
We retrospectively analyzed 153 cases of GBM. Six patients with isocitrate dehydrogenase 1 (IDH1) or H3F3A gene mutations were excluded from this study. Among the 147 cases of IDH wild-type GBM, 92 (62.6%) had the TERTp mutation. Clinical, immunohistochemical, and genetic factors (BRAF, TP53 gene mutation, CD133, ATRX expression, O6-methylguanine-DNA methyltransferase [MGMT] promoter methylation) and copy number alterations (CNAs) were investigated.

Results
GBM patients with the TERTp mutation were older at first diagnosis versus those with TERTp wild type (66.0 vs. 60.0 years, respectively, P = .034), and had shorter progression-free survival (7 vs. 10 months, respectively, P = .015) and overall survival (16 vs. 24 months, respectively, P = .017). Notably, magnetic resonance imaging performed showed that TERTp-mutant GBM was strongly associated with multifocal/distant lesions (P = .004). According to the CNA analysis, TERTp mutations were positively correlated with EGFR amp/gain, CDKN2A deletion, and PTEN deletion; however, these mutations were negatively correlated with PDGFR amp/gain, CDK4 gain, and TP53 deletion.

Conclusions
TERTp mutations were strongly correlated with multifocal/distant lesions and poor prognosis in patients with IDH wild-type GBM. Less aggressive GBM with TERTp wild type may be a distinct clinical and molecular subtype of IDH wild-type GBM.
Precise fabrication of single-atom alloy co-catalyst with optimal charge state for enhanced photocatalysis
Authors: Pan Yating , Qian Yunyang , Zheng Xusheng , Chu Sheng-Qi , Yang Yijun , Ding Chunmei , Wang Xi , Yu Shu-Hong , Jiang Hai-Long 
Published: September 2020

Abstract
While the surface charge state of co-catalysts plays a critical role for boosting photocatalysis, studies on surface charge regulation via their precise structure control remain extremely rare. Herein, metal-organic framework (MOF) stabilized bimetallic Pd@Pt nanoparticles, which feature adjustable Pt coordination environment and a controlled structure from core-shell to single-atom alloy (SAA), have been fabricated. Significantly, apart from the formation of a Mott-Schottky junction in a conventional way, we elucidate that Pt surface charge regulation can be alternatively achieved by changing its coordination environment and the structure of the Pd@Pt co-catalyst, where the charge between Pd and Pt is redistributed. As a result, the optimized Pd10@Pt1/MOF composite, which involves an unprecedented SAA co-catalyst, exhibits exceptionally high photocatalytic hydrogen production activity, far surpassing its corresponding counterparts.
A virtual sequencer reveals the dephasing patterns in error-correction code DNA sequencing
Authors: Zhou Wenxiong , Kang Li , Duan Haifeng , Qiao Shuo , Tao Louis , Chen Zitian , Huang Yanyi 
Published: September 2020

Abstract
An error-correction code (ECC) sequencing approach has recently been reported to effectively reduce sequencing errors by interrogating a DNA fragment with three orthogonal degenerate sequencing-by-synthesis (SBS) reactions. However, similar to other non-single-molecule SBS methods, the reaction will gradually lose its synchronization within a molecular colony in ECC sequencing. This phenomenon, called dephasing, causes sequencing error, and in ECC sequencing, induces distinctive dephasing patterns. To understand the characteristic dephasing patterns of the dual-base flowgram in ECC sequencing and to generate a correction algorithm, we built a virtual sequencer in silico. Starting from first principles and based on sequencing chemical reactions, we simulated ECC sequencing results, identified the key factors of dephasing in ECC sequencing chemistry and designed an effective dephasing algorithm. The results show that our dephasing algorithm is applicable to sequencing signals with at least 500 cycles, or 1000-bp average read length, with acceptably low error rate for further parity checks and ECC deduction. Our virtual sequencer with our dephasing algorithm can further be extended to a dichromatic form of ECC sequencing, allowing for a potentially much more accurate sequencing approach.
Preparing for the Quit Day: Comparing Beliefs of Nondaily Versus Daily Young Adult Smokers as They Prepare for a Quit Attempt
Authors: Hoeppner Bettina B , Hoeppner Susanne S , Carlon Hannah A , Abry Alexandra , Darville Audrey , Rohsenow Damaris J 
Published: September 2020

Abstract

Introduction
Most smoking cessation approaches are modeled on heavy daily smoking. With increasing prevalence of nondaily smoking, it may be necessary to modify these approaches for nondaily smokers.

Aims
To provide information about beliefs and attitudes relevant to smoking cessation for nondaily smokers.

Methods
Secondary analysis of two prospective studies on young adult smokers (18–24 years of age) provided brief advice to quit smoking. Measures include baseline levels of constructs relevant to smoking cessation counseling and perceived benefits of and barriers to smoking cessation.

Results
Participants (n = 40 nondaily, 122 daily smokers) were predominantly White (70% and 84%, respectively), gender-balanced (50% and 43% female), full-time college students (89% and 95%). At baseline, nondaily smokers reported lower levels of nicotine dependence (p &lt; .001; nondaily: Fagerström Test for Nicotine Dependence (FTND) = 0.8 ± 1.5, daily: FTND = 3.1 ± 1.9), lower urge to smoke (p &lt; .001), greater self-efficacy when facing external smoking stimuli (p = .03), expecting to experience fewer positive effects (reduced negative affect, p = &lt;.001, stimulation, p = .02), and valuing the importance of smoking effects less (ps &lt; .01) than daily smokers. During counseling, nondaily smokers generated both fewer benefits of cessation (Wald X2(df = 1) = 4.91, p = .027) and fewer barriers (Wald X2(df = 1) = 5.99, p =.014) than daily smokers. Withdrawal was not listed by nondaily smokers as a barrier (p &lt; .01).

Conclusions
Constructs relevant to smoking cessation for daily smokers were less salient to young nondaily smokers, compared with moderately addicted young daily smokers, as indicated by responses to standardized scales and by the generation of fewer benefits and barriers in counseling. Interventions may need to find novel ways to engage nondaily smokers, particularly young adult, in smoking cessation efforts.

Implications
This study is unique in eliciting benefits and barriers from nondaily smokers as they are about to make a quit attempt. This is a critically important point in time, as this is the point in time in which an action plan is formed and can be informed and enhanced by smoking cessation support. Our study further allowed direct comparison to daily smokers undergoing the same procedures, which allowed the identification of unique factors that may impact nondaily smokers in their quit attempt, which may guide intervention efforts. Use of a mixed method design further strengthen the rigor of this study.
Contribution of the deep chlorophyll maximum to primary production, phytoplankton assemblages and diversity in a small stratified lake
Authors: Pannard Alexandrine , Planas Dolors , Le Noac’h Philippe , Bormans Myriam , Jourdain Myriam , Beisner Beatrix E 
Published: September 2020

AbstractThis 6-month study characterized the contribution of deep chlorophyll maximum (DCM) to lake phytoplankton diversity and primary production, in relation to stratification during the ice-free season. Phytoplankton and zooplankton dynamics were examined with environmental drivers in a small stratified lake that presents vertical gradients of light and nutrients. The phytoplankton, first composed of diatoms and chrysophyceae, shifted to cyanobacteria in mid-July. With stratification increase, surface nutrient limitation appeared to favor motile species characteristic of oligotrophic environments above a deep layer of filamentous cyanobacteria, fueled by the vertical nutrient fluxes from sediment. The DCM contributed on average to 33% (but up to 60%) of total production during the strongest summer stratification period. In late summer, as stratification was eroding, the vertical gradient of nutrients was reduced, but light attenuation with depth increased. Distinct assemblages were identified between surface and deep layer with shade-adapted species. The contribution of DCM was reduced to 10%. Zooplankton community varied in conjunction with phytoplankton and stratification. Our study demonstrates no benefit of DCM for taxonomic and functional diversity and a limited contribution to total production. The depths over which phytoplankton use separate spatial niches may be lesser in a 6-m-deep lake compared with deeper stratified lakes.
Health Insurance and Mortality: Experimental Evidence from Taxpayer Outreach
Authors: Goldin Jacob , Lurie Ithai Z , McCubbin Janet 
Published: September 2020

Abstract
We evaluate a randomized outreach study in which the IRS sent informational letters to 3.9 million households that paid a tax penalty for lacking health insurance coverage under the Affordable Care Act. Drawing on administrative data, we study the effect of this intervention on taxpayers’ subsequent health insurance enrollment and mortality. We find the intervention led to increased coverage during the subsequent two years and reduced mortality among middle-aged adults over the same time period. The results provide experimental evidence that health insurance coverage can reduce mortality in the United States.
The influence of collecting patient-reported outcome measures on visit satisfaction in rheumatology clinics
Authors: Honomichl Ryan , Katzan Irene , Thompson Nicolas , Abelson Abby , Deal Chad , Rose Susannah , Lapin Brittany 
Published: September 2020

Abstract

Objectives
Patient-reported outcome measures (PROMs) can direct patient-centred care and increase patient satisfaction with the visit. The objective of this study was to assess the relationship between the collection of PROMs and visit satisfaction, as measured by the Clinician and Group Practice Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) survey.

Methods
An electronic platform for collection of patient-reported information was implemented in rheumatology clinics between August and September 2016. Adult patients were included in the study if they completed CG-CAHPS after an ambulatory visit. The pre-implementation cohort consisted of patients seen between January and June 2016; the post-implementation cohort consisted of patients seen between January and June 2017. The CG-CAHPS scores were compared between cohorts. Mixed effect models were constructed to identify predictors of visit satisfaction.

Results
Characteristics were similar between the 2117 pre- and 2380 post-implementation patients. Visit satisfaction was high in both cohorts but did not differ [odds ratio = 0.97 (95% CI: 0.79, 1.19)]. Predictors of improved satisfaction included being an established patient, being male, older age and reporting higher quality of life. However, sensitivity analyses in the post-implementation cohort suggested that implementing PROMs might convey benefits for new patients, in particular.

Conclusion
Collection of PROMs had no effect on visit satisfaction in rheumatology clinics, although there might be benefits for new patients. These largely null findings might be attributable to high satisfaction levels in our cohorts or to lack of provider review of PROM data with patients. Further research is indicated to determine the impact of provider communication of PROM results to patients on different domains of visit satisfaction.
Side Effects of Nudging: Evidence from a Randomized Intervention in the Credit Card Market
Authors: Medina Paolina C 
Published: September 2020

Abstract
This paper studies the direct and indirect effects of nudging, by means of a field experiment with a financial management platform in Brazil. Reminders for upcoming credit card payments reduced credit card late-payment fees by 14%, but increased overdraft fees in checking accounts by 9%. The unintended effect is concentrated in users with a history of overdraft use. These users experienced a net increase of 5% in total fees, while the rest experienced savings of 15%. The results provide clear insights for nudge design: like any policy action, nudges can have side effects, and one size may not fit all.
Dissimilarity in Sulcal Width Patterns in the Cortex can be Used to Identify Patients With Schizophrenia With Extreme Deficits in Cognitive Performance
Authors: Janssen Joost , Díaz-Caneja Covadonga M , Alloza Clara , Schippers Anouck , de Hoyos Lucía , Santonja Javier , Gordaliza Pedro M , Buimer Elizabeth E L , van Haren Neeltje E M , Cahn Wiepke , Arango Celso , Kahn René S , Hulshoff Pol Hilleke E , Schnack Hugo G 
Published: September 2020

Abstract
Schizophrenia is a biologically complex disorder with multiple regional deficits in cortical brain morphology. In addition, interindividual heterogeneity of cortical morphological metrics is larger in patients with schizophrenia when compared to healthy controls. Exploiting interindividual differences in the severity of cortical morphological deficits in patients instead of focusing on group averages may aid in detecting biologically informed homogeneous subgroups. The person-based similarity index (PBSI) of brain morphology indexes an individual’s morphometric similarity across numerous cortical regions amongst a sample of healthy subjects. We extended the PBSI such that it indexes the morphometric similarity of an independent individual (eg, a patient) with respect to healthy control subjects. By employing a normative modeling approach on longitudinal data, we determined an individual’s degree of morphometric dissimilarity to the norm. We calculated the PBSI for sulcal width (PBSI-SW) in patients with schizophrenia and healthy control subjects (164 patients and 164 healthy controls; 656 magnetic resonance imaging scans) and associated it with cognitive performance and cortical sulcation index. A subgroup of patients with markedly deviant PBSI-SW showed extreme deficits in cognitive performance and cortical sulcation. Progressive reduction of PBSI-SW in the schizophrenia group relative to healthy controls was driven by these deviating individuals. By explicitly leveraging interindividual differences in the severity of PBSI-SW deficits, neuroimaging-driven subgrouping of patients is feasible. As such, our results pave the way for future applications of morphometric similarity indices for subtyping of clinical populations.
How (not) to design and implement a large-scale, interdisciplinary research infrastructure
Authors: Kaufmann David , Kuenzler Johanna , Sager Fritz 
Published: September 2020

Abstract
Research is increasingly carried out in large-scale, interdisciplinary research programs that aim to tackle complex, multidimensional, and future-oriented challenges. We explore the case of the Swiss Initiative in Systems Biology (SystemsX.ch), the largest ever Swiss research program, and more specifically the partial failure of the program’s IT-project SyBIT. Apart from providing IT and data science support, SyBIT aimed to establish a common data repository. The establishment of this common data repository failed. Based on an interdisciplinary analytical framework, we propose that five explanatory factors account for this failure: a lack of demand from researchers, technological complexity of heterogeneous data formats, absence of governance decisions in favor of the data repository, interpersonal problems, and political difficulties. We conclude that for large-scale research infrastructure, the policy design is crucial for success, given that it can result in positive or negative after effects, such as user resistance versus acceptance and technological complexity versus coherence.
The evolution of the national innovation system as programmatic policy idea in Finland
Authors: Alaja Antti , Sorsa Ville-Pekka 
Published: September 2020

AbstractThis article studies the idea of a national innovation system (NIS) as a policy program. Previous research has addressed NIS as a policy idea in the context of expert discourse or as normative frames in policy discourse. The idea has not yet been studied as a policy program that explicitly coordinates public policymaking. In this article, we study the programmatic idea of NIS and its status and impacts in the coordination discourses of Finnish policymaking in 1990–2019. We find that the idea of NIS was omnipresent in Finnish policy programs of the 1990s and 2000s, but lost its programmatic status in the 2010s. We show how Finnish policymakers explicitly deployed the idea to prescribe budget allocations and new legislation. The findings suggest that the idea was given a tangible but, compared with the breadth of the idea, relatively narrow role in coordinating public policy.
Regulation of Lung Macrophage Activation and Oxidative Stress Following Ozone Exposure by Farnesoid X Receptor
Authors: Francis Mary , Guo Grace , Kong Bo , Abramova Elena V , Cervelli Jessica A , Gow Andrew J , Laskin Jeffrey D , Laskin Debra L 
Published: September 2020

AbstractInflammatory macrophages are known to contribute to ozone toxicity. Farnesoid X receptor (FXR) is a nuclear receptor involved in regulating bile acid and lipid homeostasis; it also exerts anti-inflammatory activity by suppressing macrophage NF-κB. Herein, we analyzed the role of FXR in regulating macrophage activation in the lung following ozone exposure. Treatment of wild-type (WT) mice with ozone (0.8 ppm, 3 h) resulted in increases in proinflammatory (F4/80+CD11c+CD11b+Ly6CHi) and anti-inflammatory (F4/80+CD11c+CD11b+Ly6CLo) macrophages in the lung. The accumulation of proinflammatory macrophages was increased in FXR−/− mice compared with WT mice; however, anti-inflammatory macrophage activation was blunted as reflected by reduced arginase and mannose receptor expression, a response correlated with decreased Nur77. This was associated with prolonged oxidative stress, as measured by 4-hydroxynonenal-modified proteins in the lung. Loss of FXR was accompanied by protracted increases in lung NF-κB activity and its target, inducible nitric oxide synthase in response to ozone. Levels of Tnf-α, Il-1β, Ccr2, Ccl2, Cx3cr1, and Cx3cl1 were also increased in lungs of FXR−/− relative to WT mice; conversely, genes regulating lipid homeostasis including Lxrα, Apoe, Vldlr, Abcg1, and Abca1 were downregulated, irrespective of ozone exposure. In FXR−/− mice, ozone caused an increase in total lung phospholipids, with no effect on SP-B or SP-D. Dyslipidemia was correlated with blunting of ozone-induced increases in positive end-expiratory pressure-dependent quasi-static pressure volume curves indicating a stiffer lung in FXR−/− mice. These findings identify FXR as a regulator of macrophage activation following ozone exposure suggesting that FXR ligands may be useful in mitigating inflammation and oxidative stress induced by pulmonary irritants.
Leveraging Extraction Testing to Predict Patient Exposure to Polymeric Medical Device Leachables Using Physics-based Models
Authors: Turner Paul , Elder Robert M , Nahan Keaton , Talley Anne , Shah Saloni , Duncan Timothy V , Sussman Eric M , Saylor David M 
Published: September 2020

Abstract
Toxicological risk assessment approaches are increasingly being used in lieu of animal testing to address toxicological concerns associated with release of chemical constituents from polymeric medical device components. These approaches currently rely on in vitro extraction testing in aggressive environments to estimate patient exposure to these constituents, but the clinical relevance of the test results is often ambiguous. Physics-based mass transport models can provide a framework to interpret extraction test results to provide more clinically relevant exposure estimates. However, the models require system-specific material properties, such as diffusion (D) and partition coefficients (K), to be established a priori for the extraction conditions. Using systems comprised high-density polyethylene and 4 different additives, we demonstrate that these properties can be quantified through standard extraction testing in hexane and isopropyl alcohol. The values of D and K derived in this manner were consistent with theoretical predictions for these quantities. Based on these results, we discuss both the challenges and benefits to leveraging extraction data to parameterize physics-based exposure models. Our observations suggest that clinically relevant, yet still conservative, exposure dose estimates provided by applying this approach to a single extraction measurement can be more than 100 times lower than would be measured under typical aggressive extraction conditions. However, to apply the framework on a routine basis, limiting values of D and K must be established for device-relevant systems either through the aggregation and analysis of more extensive extraction test data and/or advancements in theoretical and computational modeling efforts to predict these quantities.