bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia
Authors: Richards Alexander L , Pardiñas Antonio F , Frizzati Aura , Tansey Katherine E , Lynham Amy J , Holmans Peter , Legge Sophie E , Savage Jeanne E , Agartz Ingrid , Andreassen Ole A , Blokland Gabriella A M , Corvin Aiden , Cosgrove Donna , Degenhardt Franziska , Djurovic Srdjan , Espeseth Thomas , Ferraro Laura , Gayer-Anderson Charlotte , Giegling Ina , van Haren Neeltje E , Hartmann Annette M , Hubert John J , Jönsson Erik G , Konte Bettina , Lennertz Leonhard , Olde Loohuis Loes M , Melle Ingrid , Morgan Craig , Morris Derek W , Murray Robin M , Nyman Håkan , Ophoff Roel A ,   GROUP Investigators, van Os Jim ,   EUGEI WP2 Group,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Petryshen Tracey L , Quattrone Diego , Rietschel Marcella , Rujescu Dan , Rutten Bart P F , Streit Fabian , Strohmaier Jana , Sullivan Patrick F , Sundet Kjetil , Wagner Michael , Escott-Price Valentina , Owen Michael J , Donohoe Gary , O’Donovan Michael C , Walters James T R 
Published: May 2019

Abstract

Background
Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases.

Methods
We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases.

Results
PRS for both population IQ (P = 4.39 × 10–28) and EA (P = 1.27 × 10–26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS.

Conclusions
Cognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.
Population Pharmacokinetic Analysis of Phenytoin After Intravenous Administration of Fosphenytoin in Adult and Elderly Epileptic Patients
Authors: Higuchi Kanae , Yamashita Daiki , Kashihara Yushi , Kakara Makoto , Hirota Takeshi , Hirakawa Masaaki , Ieiri Ichiro 
Published: May 2019

Background:
Fosphenytoin, the diphosphate ester salt of phenytoin, is widely used to treat status epilepticus. The aim of this study was to develop a population pharmacokinetic (PPK) model to describe serum phenytoin concentrations after the intravenous administration of fosphenytoin in adult and elderly epileptic patients.

Methods:
Patient backgrounds, laboratory tests, and prescribed drugs were retrospectively collected from electronic medical records. Patients who received fosphenytoin were enrolled. The PPK analysis was performed using NONMEM 7.3.0 with the first-order conditional estimation method with interaction. Age, sex, laboratory tests, and coadministered drugs were selected as candidates for covariates. Significance levels for forward inclusion and backward elimination were set at 0.05 and 0.01, respectively. The study protocol was approved by the Fukuoka Tokushukai Ethics Committee.

Results:
A total of 340 serum phenytoin concentrations from 200 patients treated with fosphenytoin were available. The median age and body weight of the population were 71 years and 53.4 kg, respectively. A linear 1-compartment model with the conversion rate of fosphenytoin to phenytoin clearly described the pharmacokinetics of phenytoin after the intravenous administration of fosphenytoin. Age was detected as a covariate of clearance (CL): CL (L/h) = 1.99 × (body weight/53.4)0.75 × (age/71)−0.308. Goodness-of-fit plots revealed the high-predictive performance of the final PPK model, and systematic deviations were not observed. The final model was validated by a prediction-corrected visual predictive check and bootstrap analysis.

Conclusions:
We herein developed a PPK model to describe phenytoin concentrations after the intravenous administration of fosphenytoin. Age was identified as a significant covariate for CL.
CHANGES IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND DISEASE ACTIVITY IN TYPE 3 NEOVASCULARIZATION AFTER ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT
Authors: Han Jae Wook , Cho Han Joo , Kang Dong Hyun , Jung Seoung Heon , Park Saemi , Kim Jong Woo 
Published: May 2019

Purpose:
To investigate disease activity in patients with Type 3 neovascularization undergoing anti–vascular endothelial growth factor treatment through image analysis using optical coherence tomography angiography (OCTA).

Methods:
Thirty-nine treatment-naive eyes with Type 3 neovascularization were included in the retrospective analysis. All patients were treated with three loading injections of an anti–vascular endothelial growth factor agent, followed by further injections as needed. Changes in the Type 3 lesion were analyzed through OCTA imaging during the 12 months of follow-up.

Results:
The high-flow signal of Type 3 neovascularization on OCTA images disappeared in 46.2% eyes (19 of 39) and was persistent in 53.8% eyes (20 of 39) after loading injections. A persistent high-flow signal on OCTA after treatment was found at the sub–retinal pigment epithelium in 65.0% eyes (13 of 20), deep vascular plexus in 30.0% eyes (6 of 20), and outer neurosensory retina in 15.0% eyes (3 of 20). Eyes without lesions on OCTA images received significantly fewer injections (3.7 vs. 5.5; P = 0.016) and showed a longer retreatment-free period (mean 7.57 vs. 4.07 months; P = 0.002) during the 12-month follow-up than eyes with a persistent high-flow signal on OCTA. However, no significant between-group difference was observed in terms of improved visual acuity.

Conclusion:
Patients with Type 3 neovascularization who had no lesion on an OCTA scan after anti–vascular endothelial growth factor treatment showed a lower recurrence rate and maintained visual acuity with fewer injections than those with persistent high-flow lesions on an OCTA scan. Optical coherence tomography angiography may provide an additional biomarker for clinical guidance in the treatment and monitoring of disease activity in Type 3 neovascularization.
In Vivo Confocal Microscopy Automated Morphometric Analysis of Corneal Subbasal Nerve Plexus in Patients With Dry Eye Treated With Different Sources of Homologous Serum Eye Drops
Authors: Giannaccare Giuseppe , Pellegrini Marco , Bernabei Federico , Moscardelli Fabiana , Buzzi Marina , Versura Piera , Campos Emilio C 
Published: May 2019

Purpose:
To investigate the comparative effect of allogeneic peripheral blood serum (allo-PBS) and cord blood serum (CBS) eye drops on the status of the corneal subbasal nerve plexus in patients with dry eye disease by using an automated analysis system of in vivo confocal microscopy images.

Methods:
This prospective, randomized, double-blind study included 30 patients with severe dry eye disease assigned to receive allo-PBS (group 1) or CBS (group 2) eye drops 8 times a day for 30 days. The following in vivo confocal microscopy parameters were calculated with ACCMetrics before (visit 1 [V1]) and after treatment (visit 2 [V2]): corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, corneal nerve total branch density, corneal nerve fiber area, corneal nerve fiber width, and corneal nerve fractal dimension (CNFrD).

Results:
In overall patients, the values of corneal nerve fiber density, corneal nerve fiber length, and CNFrD significantly increased, whereas the value of corneal nerve fiber width significantly decreased at V2 compared with V1 (respectively, 20.4 ± 7.9 vs. 17.4 ± 10.1 n/mm2; 13.5 ± 4.0 vs. 12.0 ± 5.1 mm/mm2; 1.466 ± 0.046 vs. 1.475 ± 0.033; and 0.022 ± 0.002 vs. 0.023 ± 0.002; all P < 0.05). In the subanalysis according to the treatment type, the increase of CNFrD value from V1 to V2 was higher in group 2 compared with group 1 (respectively, from 1.455 ± 0.041 to 1.471 ± 0.030 and from 1.479 ± 0.050 to 1.481 ± 0.035; P = 0.030).

Conclusions:
Overall, both treatments significantly improved corneal subbasal nerve plexus parameters, and in particular, nerve density, length, width, and fractal dimension. Treatment with CBS eye drops was associated with a higher increase of CNFrD compared with allo-PBS.
Personalized Pancreatic Cancer Management
Authors: Bradley Alison , van der Meer Robert , McKay Colin 
Published: May 2019

Abstract
This review critically analyzes how machine learning is being used to support clinical decision-making in the management of potentially resectable pancreatic cancer. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, electronic searches of MEDLINE, Embase, PubMed, and Cochrane Database were undertaken. Studies were assessed using the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS) checklist. In total 89,959 citations were retrieved. Six studies met the inclusion criteria. Three studies were Markov decision-analysis models comparing neoadjuvant therapy versus upfront surgery. Three studies predicted survival time using Bayesian modeling (n = 1) and artificial neural network (n = 1), and one study explored machine learning algorithms including Bayesian network, decision trees, k-nearest neighbor, and artificial neural networks. The main methodological issues identified were limited data sources, which limits generalizability and potentiates bias; lack of external validation; and the need for transparency in methods of internal validation, consecutive sampling, and selection of candidate predictors. The future direction of research relies on expanding our view of the multidisciplinary team to include professionals from computing and data science with algorithms developed in conjunction with clinicians and viewed as aids, not replacement, to traditional clinical decision-making.
Bilateral Quadriceps Muscle Strength and Pain Correlate With Gait Speed and Gait Endurance Early After Unilateral Total Knee Arthroplasty
Authors: Suh Min Ji , Kim Bo Ryun , Kim Sang Rim , Han Eun Young , Nam Kwang Woo , Lee So Young , Park Yong Geun , Kim Won Bin 
Published: May 2019

ObjectiveThe aim of this study was to determine the correlations between objective performance-based physical function, self-reported physical function, quality of life, and gait function at 1 mo after unilateral total knee arthroplasty.DesignCross-sectional data from 195 patients who underwent unilateral primary total knee arthroplasty were analyzed. The isometric knee extensor and flexor strength of both knees, gait parameters, 6-min walk test, timed up-and-go test, timed stair-climbing test, knee flexion and extension range of motion of surgical knee, Western Ontario McMaster Universities Osteoarthritis Index pain, stiffness, and functional levels, EuroQol five-dimensions questionnaire, and visual analog scale for knee pain were assessed.ResultsIn bivariate analyses, both postoperative gait speed and gait endurance had significant positive correlations with postoperative peak torque of the extensor and flexor of both knees, cadence, stride length, and significant negative correlation with timed up-and-go, stair-climbing test ascent, stair-climbing test descent, visual analog scale, Western Ontario McMaster Universities Osteoarthritis Index pain, stiffness, and function levels. In the linear regression analyses, postoperative peak torque of the extensors of both knees and VAS for knee pain were factors correlated with postoperative gait speed and gait endurance.ConclusionsQuadriceps muscle strength of both knees and knee pain were important factors correlated with gait function early after total knee arthroplasty.
S1PR1-Associated Molecular Signature Predicts Survival in Patients with Sepsis
Authors: Feng Anlin , Rice Amanda D. , Zhang Yao , Kelly Gabriel T. , Zhou Tong , Wang Ting 
Published: May 2019

ABSTRACT

Background:
Sepsis is a potentially life-threatening complication of an underlying infection that quickly triggers tissue damage in multiple organ systems. To date, there are no established useful prognostic biomarkers for sepsis survival prediction. Sphingosine-1-phosphate (S1P) and its receptor S1P receptor 1 (S1PR1) are potential therapeutic targets and biomarkers for sepsis, as both are active regulators of sepsis-relevant signaling events. However, the identification of an S1PR1-related gene signature for prediction of survival in sepsis patients has yet to be identified. This study aims to find S1PR1-associated biomarkers which could predict the survival of patients with sepsis using gene expression profiles of peripheral blood to be used as potential prognostic and diagnostic tools.

Methods:
Gene expression analysis from sepsis patients enrolled in published datasets from Gene Expression Omnibus was utilized to identify both S1PR1-related genes (co-expression genes or functional-related genes) and sepsis survival-related genes.

Results:
We identified 62-gene and 16-gene S1PR1-related molecular signatures (SMS) associated with survival of patients with sepsis in discovery cohort. Both SMS genes are significantly enriched in multiple key immunity-related pathways that are known to play critical roles in sepsis development. Meanwhile, the SMS performs well in a validation cohort containing sepsis patients. We further confirmed our SMSs, as newly developed gene signatures, perform significantly better than random gene signatures with the same gene size, in sepsis survival prognosis.

Conclusions:
Our results have confirmed the significant involvement of S1PR1-dependent genes in the development of sepsis and provided new gene signatures for predicting survival of sepsis patients.
Cardiogenic Shock Following Acute Myocardial Infarction: What's New?
Authors: Pepe Martino , Bortone Alessandro Santo , Giordano Arturo , Cecere Annagrazia , Burattini Osvaldo , Nestola Palma Luisa , Patti Giuseppe , Di Cillo Ottavio , Signore Nicola , Forleo Cinzia , Favale Stefano 
Published: May 2019

ABSTRACT
Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion primarily due to cardiac dysfunction. This condition is the most common cause of death in patients affected by acute myocardial infarction (AMI). Despite early revascularization, prompt optimal medical therapy, and up-to-date mechanical circulatory supports, mortality of patients with CS remains high.
The objective of this review is to summarize epidemiology, pathophysiology, and treatment options of CS in light of the new European Society of Cardiology (ESC) recommendations. The latest European guidelines on myocardial revascularization have reviewed the previous guidelines with respect to early multivessel revascularization and routine use of intra-aortic balloon pump (IABP) in patients with AMI-related CS.
Most of the current evidences come partly from randomized trials, but mostly from observational registries because of the difficulty to test different treatments in this life-threatening clinical setting.
Some of the latest studies highlight the potential crucial benefit of newly introduced mechanical circulatory support devices, although evidences are not sufficient to definitely assess the benefit/risk ratio of the different systems.
Many questions remain unanswered in this field, and further trials are advocated to better elucidate the best medical, reperfusion, and circulatory support approaches aimed to improve the poor prognosis of patients with CS after AMI.
Simultaneous regulation of cytokinetic furrow and nucleus positions by cortical tension contributes to proper DNA segregation during late mitosis
Authors: Pacquelet Anne , Jousseaume Matthieu , Etienne Jocelyn , Michaux Grégoire 
Published: May 2019

AbstractCoordinating mitotic spindle and cytokinetic furrow positioning is essential to ensure proper DNA segregation. Here we present a novel mechanism, which corrects DNA segregation defects due to cytokinetic furrow mispositioning. We show that DNA segregation defects following the abnormal displacement of the cytokinetic furrow towards the anterior side of C. elegans one-cell embryos are unexpectedly corrected at the end of cytokinesis. This correction relies on the concomitant displacement of the furrow and of the anterior nucleus towards the posterior and anterior poles, respectively. It also coincides with cortical blebbing and an anteriorly directed flow of cytoplasmic particles. While microtubules contribute to nuclear displacement, relaxation of an excessive tension at the anterior cortex plays a central role in the correction process and simultaneously regulates cytoplasmic flow as well as nuclear and furrow displacements. This work thus reveals the existence of a so far uncharacterized correction mechanism, which is critical to correct DNA segregation defects due to cytokinetic furrow mispositioning.
Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance
Authors: Jiang Dong , Wang Jianghua , Zhao Xuesen , Li Yuxin , Zhang Qun , Song Chuan , Zeng Hui , Wang Xianbo 
Published: May 2019

AbstractBackground & AimsTenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug-resistant hepatitis B virus (MDR HBV) and few clinical cases with confirmed TDF-resistance have been reported to date. We reported a quadruple mutant which showed moderate resistant to TDF.Methods and resultsViral rebound was reported in a patient with chronic hepatitis B who underwent TDF monotherapy and harbored a quadruple mutant consisting of classic ETV-resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52-fold higher half maximal effective concentration than that of wild-type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy.ConclusionAn rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential NA treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF resistant mutant. Our studies provide novel insights into the treatment of NA-naïve patients as well as patients with TDF resistance.
The effect of tongue-tie application on stress responses in resting horses
Authors: Marsh Laura , McGreevy Paul , Hazel Susan , Santos Luiz , Hebart Michelle , Franklin Samantha 
Published: May 2019

AbstractTongue-ties (TT) are commonly applied to both Standardbred and Thoroughbred racehorses to increase control, by preventing them from getting their tongue over the bit, and as a conservative treatment for equine respiratory conditions, principally dorsal displacement of the soft palate. This study investigated responses to TT application in horses, at rest, using both behavioural (head-tossing, ear position, gaping and lip licking) and physiological (salivary cortisol concentrations, eye surface temperature and heart rate) indices. Twelve Standardbred horses (six of which were naïve to TT) were used in a randomised crossover design. The study comprised 3 phases; Phase 1 (Baseline), Phase 2 (Treatment), and Phase 3 (Recovery). At phase 2, tongue tie application (TTA) was performed using a rubber band that was looped around the tongue and secured to the mandible for 20 minutes. The control treatment (C) incorporated 30 secs of tongue manipulation, at the start of the 20 min, however no TT was applied. Behaviours (head-tossing, ear position, mouth gaping and lip-licking) and heart rate (HR) were recorded for the duration of the study and analysed in ten minute intervals. Salivary samples were taken at the end of each phase for subsequent cortisol assays and infrared thermography images were taken of each eye at 5-minute intervals. Statistical analyses were performed in SPSS using linear mixed effects models and repeated measures general linear models, to determine differences between treatments and within treatments, over time. Compared to control, there was more head-tossing/shaking (p<0.001), gaping (p<0.001) and backwards ear position (p<0.001) and less forward ear position (p<0.001) during TTA, in Phase 2. Horses with previous experience of TT showed more head-tossing (p=0.040) and gaping (p=0.030) than naïve horses. Lip-licking was more frequent after TTA treatment than control, during Phase 3 (p<0.001). Salivary cortisol concentrations increased after TTA (1846.1pg/mL ± 478.3pg/mL vs 1253.6pg/mL ± 491.6pg/mL, p=0.047). Mean HR, and mean right and left eye temperature did not differ significantly between treatments in any phase (all p> 0.05). The findings of this study suggest the application of a tongue-tie causes changes to both behavioural and physiological parameters suggestive of a stress-related response. Further research is needed that will enable racing and sport horse regulatory bodies to make informed decisions about the appropriate use of tongue-ties in horses.