bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of discontinuation v. maintenance of antipsychotic medication on relapse rates in patients with remitted/stable first-episode psychosis: a meta-analysis
Authors: Kishi Taro , Ikuta Toshikazu , Matsui Yuki , Inada Ken , Matsuda Yuki , Mishima Kazuo , Iwata Nakao 
Published: June 2018

AbstractBackgroundDiscontinuation of antipsychotics predisposes patients with remitted/stable first-episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance.MethodsThis meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18–24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model.ResultsTen RCTs were identified (n = 776; mean study duration, 18.6 ± 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18–24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant).ConclusionsMaintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for ⩾2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18–24 months) did not experience a relapse.
Some Properties of Platelet Cofactor I Concentrates of Bovine Origin
Authors: Baker William J. , Seegers Walter H. 
Published: June 2018

SummaryPlatelet cofactor I preparations from bovine plasma were studied from the viewpoint of stability in the presence of chemicals selected strategically. The preparations were of high quality having about 86 per cent of the protein as one component by ultracentrifuge analysis. The activity was easily destroyed with hydrogen peroxide, sodium sulfite, phenylhydrazine, formalin, acetone, and by the process of freeze drying. The activity was not lost in the presence of oxygen, ascorbic acid, cysteine, merthiolate, parachloromercuribenzoate or 0.5 per cent phenol. In the native plasma the activity is not adsorbed on barium carbonate, barium sulfate, or magnesium hydroxide. Nor is it destroyed by ether; but, in purified form it is adsorbed on these adsorbants and is destroyed by ether. In the purified preparations the activity was not adsorbed on IRC-50 resin thus making it possible to use this adsorbant to remove any thrombin that might be added to a platelet cofactor I preparation. By this technic it was possible to show that thrombin alone does not easily destroy platelet cofactor I activity.
The need for an alternative method to determine intravascular volumes
Authors: Lobigs L. M. , Peeling P. , Dawson B. , Schumacher Y. O. 
Published: June 2018

AbstractIt is well described that numerous environmental factors, including exercise, modulate plasma volume (PV). These modulations prove problematic when a number of haematological markers are measured as a concentration in blood plasma. A primary example is haemoglobin concentration ([Hb]), a marker of erythropoiesis commonly used within medicine and also used to detect blood doping. Natural changes in PV can confound [Hb] values when a volume change is detected rather than a true change in haemoglobin mass (Hbmass) (e.g. volume expansion resulting in a [Hb] decrease and pseudo‐anemia vs. Hbmass decline resulting in anaemia). Currently, there is no simple solution to correct for PV shifts, and this has proven problematic when monitoring volumetric health markers in clinical and anti‐doping settings. This narrative review explores the influence that PV shifts have on volumetric biomarkers, such as [Hb]. The progressive expansion in PV observed during multi‐day endurance events will be summarised, and the observed impact PV variance has on concentration‐based markers will be quantified. From this, the need for alternative methods to correct [Hb] for volume fluctuations is highlighted. Available methods for calculating intravascular volumes are then discussed, with a focus on a recently developed approach using a panel of ‘volume descriptive’ biomarkers from a standard blood test. Finally, the practical applications of this novel PV blood test within both anti‐doping and clinical settings will be examined.
Does the Alfvén wave disrupt the large-scale magnetic cloud structure?
Authors: Raghav Anil N , Kule Ankita 
Published: June 2018

ABSTRACT
Alfvén waves are primal and pervasive in space plasmas and significantly contribute to microscale fluctuations in the solar wind and some heliospheric processes. Here, we demonstrate the first observable distinct feature of Alfvén wave while propagating from magnetic cloud to trailing solar wind. The Walén test is used to confirm their presence in selected regions. The amplitude ratio of inward to outward Alfvén waves is employed to establish their flow direction. The dominant inward flow is observed in magnetic cloud whereas trailing solar wind shows the dominant outward flow of Alfvén waves. The observed reduction in Walén slope and correlation coefficient within magnetic cloud suggest (i) the simultaneous presence of an inward and outward Alfvén waves and/or (ii) a possibility of magnetic reconnection and/or (iii) development of thermal anisotropy, and/or (iv) dissipation of Alfvénic fluctuations. The study implies that either the Alfvén waves dissipate in the magnetic cloud or their presence can lead to a disruption of the magnetic cloud structure.
Responsible research and innovation in Europe: A cross-country comparative analysis
Authors: Mejlgaard Niels , Bloch Carter , Madsen Emil Bargmann 
Published: June 2018

Abstract
The objective of this article is to contribute to the emerging attempts to foster empirical, quantitative approaches to Responsible Research and Innovation (RRI), and to provide a low-resolution map of the European RRI landscape, which can serve as a vehicle for international learning. The article presents indicators of RRI aimed at characterising countries. It examines the empirical structure of the data collected in the ‘Monitoring the evolution and benefits of Responsible Research and Innovation’ (MoRRI) project and reports patterns across Europe. Factor analysis is applied to identify 11 empirically-anchored dimensions of RRI. Based on indices for these dimensions, cluster analysis reveals four distinct clusters of countries. These results point to diversity regarding the empirically-manifest components of RRI as well as diversity in the RRI profiles of the 28 European Union Member States.
Intraindividual and Interindividual Variability of Olanzapine Trough Concentrations in Patients Treated With the Long-Acting Injectable Formulation
Authors: Baldelli Sara , Mauri Massimo C. , Di Pace Chiara , Paletta Silvia , Reggiori Alessandra , Rovera Chiara , Clementi Emilio , Cattaneo Dario 
Published: June 2018

Abstract

Background
A long-acting injectable (LAI) formulation of olanzapine has been developed as an alternative to oral regimens. A therapeutic range of 20 to 80 ng/mL for oral olanzapine trough concentrations has been proposed. Here, we sought to investigate the intraindividual and interindividual variability of olanzapine concentrations with time in patients on maintenance therapy with the LAI formulation carried out in the routine clinical practice.

Methods
To address this issue, we carried out a retrospective analysis of therapeutic drug monitoring of olanzapine concentrations in 21 schizophrenic patients on maintenance LAI olanzapine. Drug concentrations were correlated with LAI olanzapine doses, duration of treatment, and main clinical characteristics.

Results
Fifty percent of the patients had olanzapine trough concentrations lower than 20 ng/mL. Only drug doses significantly correlated with olanzapine exposure. Mean interindividual and intraindividual coefficients of variations of olanzapine concentrations were 56% (range, 21%–97%) and 34% (range, 15%–69%), respectively.

Conclusions
We have documented that, in a real-life setting, a large proportion of patients treated with olanzapine LAI had drug trough concentrations of less than 20 ng/mL; wide intraindividual and interindividual variability of olanzapine concentrations has been also observed. Our results could provide the rationale for the design of larger prospective, concentration-controlled clinical trials specifically designed with the goal to identify ad hoc therapeutic ranges of drug concentrations for olanzapine LAI.
Earphone and Aided Word Recognition Differences in Cochlear Implant Candidates
Authors: McRackan Theodore R. , Fabie Joshua E. , Burton Jane A. , Munawar Suqrat , Holcomb Meredith A. , Dubno Judy R. 
Published: June 2018

Objective:
Compare word recognition scores for adults undergoing cochlear implant evaluations (CIE) measured using earphones and hearing aids.

Study Design:
Retrospective review of data obtained during adult CIEs.

Setting:
Tertiary cochlear implant center.

Patients:
Two hundred eight ears in 183 subjects with greater than 10% word recognition scores measured with earphones.

Interventions/Main Outcomes Measured:
Preoperative pure-tone thresholds and word recognition scores measured with earphones and hearing aids.

Results:
A review of audiological data obtained from 2012 to 2017 during adult CIEs was conducted. Overall, a weak positive correlation (r = 0.33, 95% confidence interval 0.17–0.40, p < 0.001) was observed between word recognition scores measured with earphones and hearing aids. Earphone to aided differences (EAD)1 ranged from −38 to +72% (mean 14.3 ± 19.9%). Consistent with EADs, 108 ears (51.9%) had earphone scores that were significantly higher than aided word recognition scores (+EAD), as determined by 95% confidence intervals; for 14 ears (6.7%), earphone scores were significantly lower than aided scores (−EAD). Moreover, of the patients with earphone word recognition scores ≥50%, 82.6% were CI candidates based on aided AzBio+10 dB SNR scores.

Conclusion:
These results demonstrate the limited diagnostic value of word recognition scores measured under earphones for patients undergoing CIE. Nevertheless, aided word recognition is rarely measured before CIEs, which limits the information available to determine CI candidacy and referral for CIEs. Earlier and routine measurement of aided word recognition may help guide clinical decision making by determining the extent to which patients are achieving maximum benefit with their hearing aids or should consider cochlear implantation.
Real-World Study on Sofosbuvir-based Therapies in Asian Americans With Chronic Hepatitis C
Authors: Pan Calvin Q. , Tiongson Benjamin C. , Hu Ke-Qin , Han Steven-Huy B. , Tong Myron , Chu Danny , Park James , Lee Tai Ping , Bhamidimarri Kalyan Ram , Ma Xiaoli , Xiao Pei Ying , Mohanty Smruti R. , Wang Dan 
Published: June 2018

Background:
Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans.

Methods:
Eligible Asian Americans patients with CHC who had posttreatment follow-up of 24 weeks for SOF -based therapies from December 2013 to June 2017 were enrolled from 11 sites across the United States. The primary endpoint was sustained virologic response (SVR) rates at posttreatment weeks 12 and 24. Secondary endpoints were to evaluate safety by tolerability and adverse events (AEs).

Results:
Among 231 patients screened, 186 were enrolled. At baseline, 31% (57/186) patients were cirrhotic, 34% (63/186) were treatment experienced. Most of the subjects (42%, 79/186) received ledispavir/SOF therapy. The overall SVR12 was 95%, ranging from 86% in genotype (GT) 1b on SOF+ribavirin to 100% in GT 1b patients on ledipasvir/SOF at subgroup analyses. SVR12 was significantly lower in cirrhotic than in noncirrhotic patients [88% (50/57) vs. 98% (126/129), P<0.01]. Stratified by GT, SVR12 were: 96% (43/45) in GT 1a; 93% (67/72) in GT 1b; 100% (23/23) in GT 2; 90% (19/21) in GT 3; 100% (1/1) in GT 4; 83% (5/6) in GT 5; and 100% (16/16) in GT 6. Cirrhotic patients with treatment failure were primarily GT 1, (GT 1a, n=2; GT 1b, n=4) with 1 GT 5 (n=1). Patients tolerated the treatment without serious AEs. Late relapse occurred in 1 patient after achieving SVR12.

Conclusions:
In Asian Americans with CHC, SOF-based regimens were well tolerated without serious AEs and could achieve high SVR12 regardless of hepatitis C viral infection GT.
Time-varying Readmission Diagnoses During 30 Days After Hospitalization for COPD Exacerbation
Authors: Goto Tadahiro , Faridi Mohammad K. , Camargo Carlos A. , Hasegawa Kohei 
Published: June 2018

Objective:
To investigate the longitudinal changes in principal readmission diagnoses within 30 days after hospitalization for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Study Setting:
Medicare claims data, 2010–2012.

Study Design:
Retrospective cohort study.

Data Collection Methods:
We identified AECOPD hospitalizations aged 65 years and above, and examined the principal 30-day readmission diagnoses (respiratory related, cardiac related, and other conditions). We also constructed Joinpoint regression models to test whether patients with each of the 3 major readmission conditions had a unique temporal pattern of readmission during the 30-day period.

Principal Findings:
Among 76,697 index hospitalizations with AECOPD, 14,090 (18.4%) were readmitted within 30 days. Respiratory-related conditions accounted for 55% of readmissions. The proportion of respiratory-related conditions as the readmission diagnosis decreased from postdischarge day 1 to day 8 (4.0% decrease), and then increased thereafter (13.2% increase; P=0.06). Cardiac-related conditions had a similar nonlinear trend with an inflection point at day 6 (P=0.02), with a subsequent downward trend from day 22 (P=0.01). By contrast, the other conditions increased from day 1 to day 6 (15.0% increase), and then significantly decreased (28.8% decrease; P=0.04).

Conclusions:
The proportions of principal discharge diagnosis of readmission changed significantly at around postdischarge day 7. Our findings advance research into identification of the underlying mechanisms and development of targeted interventions to prevent readmissions.
VGLUT2 functions as a differential marker for hippocampal output neurons
Authors: Wozny Christian , Beed Prateep , Nitzan Noam , Pössnecker Yona , Rost Benjamin R. , Schmitz Dietmar 
Published: June 2018

AbstractThe subiculum is the gatekeeper between the hippocampus and cortical areas. Yet, the lack of a pyramidal cell-specific marker gene has made the analysis of the subicular area very difficult. Here we report that the vesicular-glutamate transporter 2 (VGLUT2) functions as a specific marker gene for subicular burst-firing neurons, and demonstrate that VGLUT2-Cre mice allow for Channelrhodopsin-2 (ChR2)-assisted connectivity analysis.
DISC1 regulates N-Methyl-D-Aspartate receptor dynamics: Abnormalities induced by a Disc1 mutation modelling a translocation linked to major mental illness
Authors: Malavasi Elise L.V. , Economides Kyriakos D. , Grünewald Ellen , Makedonopoulou Paraskevi , Gautier Philippe , Mackie Shaun , Murphy Laura C. , Murdoch Hannah , Crummie Darragh , Ogawa Fumiaki , McCartney Daniel L. , O’Sullivan Shane T. , Burr Karen , Torrance Helen S. , Phillips Jonathan , Bonneau Marion , Anderson Susan M. , Perry Paul , Pearson Matthew , Constantinides Costas , Davidson-Smith Hazel , Kabiri Mostafa , Duff Barbara , Johnstone Mandy , Greg Polites H. , Lawrie Stephen , Blackwood Douglas , Semple Colin A. , Evans Kathryn L. , Didier Michel , Chandran Siddharthan , McIntosh Andrew M. , Price David J. , Houslay Miles D. , Porteous David J. , Kirsty Millar J. 
Published: June 2018

ABSTRACTThe neuromodulatory gene DISC1 is disrupted by a t(1;11) translocation that is highly penetrant for schizophrenia and affective disorders, but how this translocation affects DISC1 function is incompletely understood. N-Methyl-D-Aspartate receptors (NMDAR) play a central role in synaptic plasticity and cognition, and are implicated in the pathophysiology of schizophrenia through genetic and functional studies. We show that the NMDAR subunit GluN2B complexes with DISC1-associated trafficking factor TRAK1, while DISC1 interacts with the GluN1 subunit and regulates dendritic NMDAR motility in cultured mouse neurons. Moreover, in the first mutant mouse that models DISC1 disruption by the translocation, the pool of NMDAR transport vesicles and surface/synaptic NMDAR expression are increased. Since NMDAR cell surface/synaptic expression is tightly regulated to ensure correct function, these changes in the mutant mouse are likely to affect NMDAR signalling and synaptic plasticity. Consistent with these observations, RNASeq analysis of translocation carrier-derived human neurons indicates abnormalities of excitatory synapses and vesicle dynamics. RNASeq analysis of the human neurons also identifies many differentially expressed genes previously highlighted as putative schizophrenia and/or depression risk factors through large-scale genome-wide association and copy number variant studies, indicating that the translocation triggers common disease pathways that are shared with unrelated psychiatric patients. Altogether our findings suggest that translocation-induced disease mechanisms are likely to be relevant to mental illness in general, and that such disease mechanisms include altered NMDAR dynamics and excitatory synapse function. This could contribute to the cognitive disorders displayed by translocation carriers.
Parallel genome-wide CRISPR analysis identifies a role for heterotypic ubiquitin chains in ER-associated degradation
Authors: Leto Dara E. , Morgens David W. , Zhang Lichao , Walczak Christopher P. , Elias Joshua E. , Bassik Michael C. , Kopito Ron R. 
Published: June 2018

SummaryThe ubiquitin proteasome system (UPS) maintains the integrity of the proteome and controls the abundance of key regulators of cellular function by selective protein degradation, but how foldingdefective proteins in the secretory system are selected from the large and diverse constellation of membrane and secretory proteins and efficiently delivered to proteasomes in the cytosol is not well understood. To determine the basis of substrate selectivity in human cells, we developed a transcriptional shut off approach to conduct parallel, unbiased, genome-wide CRISPR analysis of structurally and topologically diverse ER-associated degradation (ERAD) clients. Highly quantitative screen metrics allowed precise dissection of entire pathways, enabling identification of unique substrate-specific combinations of recognition and ubiquitin conjugation modules. Our analysis identified cytosolic ubiquitin conjugating machinery that has not been previously linked to ERAD but collaborates with membrane-integrated ubiquitin ligases to conjugate branched or mixed ubiquitin chains to promote efficient and processive substrate degradation.
Automethylation of PRC2 fine-tunes its catalytic activity on chromatin
Authors: Lee Chul-Hwan , Granat Jeffrey , Yu Jia-Ray , LeRoy Gary , Stafford James , Reinberg Danny 
Published: June 2018

AbstractThe catalytic activity of PRC2 is central to maintain transcriptional repression by H3K27me3-decorated facultative heterochromatin in mammalian cells. To date, multiple factors have been reported to regulate PRC2 activity. Here, we demonstrate that PRC2 methylates itself on EZH1/2 and SUZ12 subunits, with EZH1/2-K514 being the major automethylation site in cells. The functional studies of automethylation on EZH2 indicate automethylation as a self-activating mechanism for PRC2 in the absence of stimulatory cofactors like AEBP2. Together, our study reveals PRC2 automethylation as a novel regulatory mechanism of PRC2 activity on chromatin.
Virtual Verification and Validation of Automotive System
Authors: Safar Mona , El-Moursy Magdy A. , Abdelsalam Mohamed , Bakr Ayman , Khalil Keroles , Salem Ashraf 
Published: June 2018

An integrated framework for Virtual Verification and Validation (VVV) for a complete automotive system is proposed. The framework can simulate/emulate the system on three levels: System on Chip (SoC), Electronic control unit (ECU) and system level. The framework emulates the real system including hardware (HW) and software (SW). It enhances the automotive V-cycle and allows co-development of the automotive system SW and HW. The procedure for debugging AUTOSAR application on the virtual platform (VP) is shown. SW and HW profiling is feasible with the presented methodology. Verification and validation of automotive embedded SW is also presented. The proposed methodology is efficient as the system complexity increases which shortens the development cycle of automotive system. It also provides fault injection capability. With HW emulation, co-debugging mechanism is demonstrated. A case study covering the framework capability is presented. The case study demonstrates the proposed framework and methodology to design, simulate, trace, profile and debug AUTOSAR SW using VPs.
Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta‐Analysis, and New Insights From the CLOSE Study
Authors: Turc Guillaume , Calvet David , Guérin Patrice , Sroussi Marjorie , Chatellier Gilles , Mas Jean‐Louis ,   the CLOSE Investigators
Published: June 2018

Background

We conducted a systematic review and meta‐analysis of randomized controlled trials (
RCT
s) comparing patent foramen ovale (
PFO
) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with
PFO
‐associated cryptogenic stroke.

Methods and Results

We searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (
RR
s) were calculated in random‐effects meta‐analyses.
PFO
closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6
RCT
s;
RR
=0.36, 95%
CI
: 0.17–0.79; I
2
=59%). The effect of
PFO
closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (
RR
=0.27, 95%
CI
, 0.11–0.70; I
2
=42%) compared with patients without these anatomical features (
RR
=0.80, 95%
CI
, 0.43–1.47; I
2
=12%). Major complications occurred in 2.40% (95%
CI
, 1.03–4.25; I
2
=77%) of procedures. New‐onset atrial fibrillation was more frequent in patients randomized to
PFO
closure versus antithrombotic therapy (
RR
=4.33, 95%
CI
, 2.37–7.89; I
2
=14%). One
RCT
compared
PFO
closure versus anticoagulation (353 patients; hazard ratio=0.14, 95%
CI
, 0.00–1.45) and 2
RCT
s compared
PFO
closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95%
CI
, 0.05–0.63; I
2
=12%). Three
RCT
s compared anticoagulation versus antiplatelet therapy, with none showing a significant difference.

Conclusions

PFO
closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle‐aged patients.
PFO
closure was associated with an increased risk of atrial fibrillation.