bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vortioxetine Disposition in Obesity
Authors: Greenblatt David J. , Harmatz Jerold S. , Chow Christina R. 
Published: March 2018

AbstractBackgroundObesity and depression are common comorbid conditions. The objective of the study was to evaluate the effect of obesity on the pharmacokinetics of the serotonergic antidepressant vortioxetine.MethodsVortioxetine pharmacokinetics were evaluated in 16 otherwise healthy obese volunteers (mean weight, 119 kg; mean body mass index (BMI) 41.8 kg/m2) and in 14 normal-weight subjects (mean weight, 68 kg; mean BMI, 23.0 kg/m2) matched for age. All subjects received a single 5-mg oral dose of vortioxetine once daily for 29 days. Pre-dose plasma vortioxetine concentrations were measured during the 29 days of dosing, and during a 4-week washout period after the last dose. Full 24-hour profiles were obtained after the first and last doses.ResultsVortioxetine accumulated extensively over the 29 days; the accumulation ratio was not significantly different between obese and control groups (means: 5.24 and 4.46, respectively). Steady-state concentration (Css) and steady-state clearance also did not differ between groups. However mean washout half-life (T1/2) was significantly prolonged in obese vs. control subjects (3.26 days vs. 2.21 days,P< 0.01). Up to 89% of the individual variability in T1/2was explained by the product of Cssand numeric indicators of the degree of obesity.ConclusionsThe half-life of vortioxetine washout after discontinuation of therapy is significantly prolonged in obese individuals compared to normal weight controls. To avoid a potential risk of serotonin syndrome, obese patients who plan to change their medication from vortioxetine to a monoamine oxidase inhibitor (MAOI) should extend the time between vortioxetine discontinuation and MAOI initiation beyond what is recommended in the product label.
Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy Women
Authors: Kruger Tillmann H.C. , Deiter Frank , Zhang Yuanyuan , Jung Stefanie , Schippert Cordula , Kahl Kai G. , Heinrichs Markus , Schedlowski Manfred , Hartmann Uwe 
Published: March 2018

Abstract

Purpose
The neuropeptide oxytocin (OXT) has a variety of physiological functions in maternal behavior and attachment including sexual behavior. Based on animal research and our previous human studies, we set out to investigate intranasal administration of OXT and hypothesized that OXT should be able to modulate sexual function in women.

Methods
In a double-blind, placebo-controlled, crossover laboratory setting, the acute effects of intranasal administered OXT (24 international units) on sexual drive, arousal, orgasm, and refractory aspects of sexual behavior were analyzed in 27 healthy females (mean age ± SD, 27.52 ± 8.04) together with physiological parameters using vaginal photoplethysmography.

Findings
Oxytocin administration showed no effect on subjective sexual parameters (eg, postorgasmic tension; P = 0.051). Physiological parameters (vaginal photoplethysmography amplitude and vaginal blood volume) showed a response pattern towards sexual arousal but were not affected by OXT.

Implications
Using a well-established laboratory paradigm, we did not find that intranasal OXT influences female sexual parameters. Also, sexual drive and other functions were not affected by OXT. These findings indicate that OXT is not able to significantly increase subjective and objective parameters of sexual function in a setting with high internal validity; however, this might be different in a more naturalistic setting.
Maternal Antidepressant Use During Pregnancy and the Risk of Attention-Deficit/Hyperactivity Disorder in Children
Authors: Uguz Faruk 
Published: March 2018

Abstract

Purpose
This study reviewed the current literature examining the potential relationship between use of antidepressants during pregnancy and attention-deficit/hyperactivity disorder (ADHD) in children.

Methods
PubMed was searched for English language reports between January 1, 1995, and July 31, 2017, by using combinations of the key words pregnancy, antidepressants, selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), children, offspring, and ADHD. Studies that reported association between ADHD in children and use of antidepressant in pregnant women were included in the review.

Results
A total of 7 relevant studies that met the review criteria were examined. The studies reported that compared with nonusers adjusted risks of ADHD in children were 1.2 to 1.6 for the use of any antidepressant, 0.91 to 1.66 for selective serotonin reuptake inhibitors, 1.1 to 1.4 for selective serotonin-norepinephrine reuptake inhibitors, and 1.1 to 1.8 for tricyclic antidepressants. There was some scientific evidences suggesting a connection between antidepressant use during all trimesters of pregnancy and increased risk of ADHD in children. In addition, the study results suggest that underlying maternal anxiety or depressive disorders may also contribute to increased risk of ADHD.

Implications
Although some studies have suggested a moderately increased risk of ADHD in children with maternal antidepressant use during pregnancy, based on limitations and results of the studies, this review concluded that there is no strong evidence to suggest a causal link.
The Relationship of Prosthetic Sock Ply Thickness to Percentage of Transtibial Limb Volume Outside of the Socket
Authors: Jasken Jenna , Hall Michelle 
Published: March 2018

ABSTRACT

Introduction
Prosthetic socks are typically used to accommodate volume fluctuations throughout the day. Clinically, prosthetists often use sock ply thickness to assess the fit of a prosthetic socket and the amount of volume reduction necessary for the next socket iteration. This is done by using various sock plies to determine the proper socket fit. The amount of volume reduction needed for a specific sock ply fit is unclear.

Objective
This preliminary study aimed to measure the relationship between sock ply and percentage of volume change.

Methods
The Rodin4D scanner was used to scan three transtibial sample foam models. Each model had an appropriately sized liner, which was scanned as a baseline measurement. Each sock ply combination (one, two, three, five, one + one, one + two, two + three, two + one, and three + two) was scanned six times per model. Scan order was randomly assigned for each model.

Results
Significant differences in volume change were found between one-ply (5.188%) and three-ply (10.42%) and five-ply (8.83%) socks, but not two-ply socks (7.15%). A significant volume increase was shown for the use of multiple socks (three + two ply, 18.33%, or two + three ply, 18.33%) compared with a single five-ply sock (8.83%). However, no significant differences were found in a similar comparison of a single three-ply sock (10.42%) versus the one + two–ply (11.68%) or two + one–ply (11.57%) socks.

Conclusion
Our results showed that the use of multiple socks for the same ply, specifically the order of socks donned for the two + three ply and three + two ply, resulted in greater volume than a single sock of the same ply (i.e., five ply). The volumetric change for five-ply is significantly different from one-ply, but not from two-ply and three-ply socks. A limitation of this study was that the scans were completed on foam models with the point of measurement at the distal patella causing potential for the posterior wall to be outside of the socket. This may change on a human subject. The percentage of volume changes based on sock ply thickness that were determined from this study may be used as a starting point for prosthetists during modifications, but further research is needed to determine how this volume changes within the socket.
Anterior Cruciate Ligament Injuries in the National Hockey League: Epidemiology and Performance Impact
Authors: Longstaffe Robert , Leiter Jeff , MacDonald Peter 
Published: March 2018

Objective:
To determine the incidence of anterior cruciate ligament (ACL) injuries in the National Hockey League (NHL) and to examine the effects of this injury on return-to-play status and performance.

Design:
Case series; level of evidence, 4.

Methods:
This was a 2-phase study. Phase I used the NHL electronic injury surveillance system and Athlete Health Management System to collect data on ACL injuries and man games lost over 10 seasons (2006/2007-2015/2016). Data collected in phase I were received in deidentified form. Phase II examined the performance impact of an ACL injury. Players were identified through publically available sources, and performance-related statistics were analyzed. Data collected in phase II were not linked to data collected in phase I. A paired t test was used to determine any difference in the matching variables between controls and cases in the preinjury time period. A General linear model (mixed) was used to determine the performance impact.

Results:
Phase I: 67 ACL injuries occurred over 10 seasons. The incidence for all players was 0.42/1000 player game hours (forward, 0.61; defenseman, 0.32, goalie, 0.08) and by game exposure was 0.2/1000 player game exposures (forward, 0.33; defenseman, 0.11; goalie, 0.07). Forwards had a greater incidence rate of ACL tears with both game hours and game exposures when compared with defensemen and goalies (P < 0.001, <0.001; P = 0.008, <0.001, respectively). Phase II: 70 ACL tears (60 players) were identified. Compared with controls, players who suffered an ACL tear demonstrated a decrease in goals/season (P < 0.04), goals/game (P < 0.015), points/season (0.007), and points/game (0.001). Number of games and seasons played after an ACL injury did not differ compared with controls (P = 0.068, 0.122, respectively).

Conclusions:
Anterior cruciate ligament injuries occur infrequently, as it relates to other hockey injuries. Despite a high return to play, the performance after an ACL injury demonstrated a decrease in points and goals per game and per season.
The Efficiency of a Multicomponent Training for Prospective Memory Among Healthy Older Adults
Authors: Farzin Azin , Ibrahim Rahimah , Madon Zainal , Basri Hamidon 
Published: March 2018

ObjectiveThe main objective of the present trial was to evaluate the efficiency of a preventative multicomponent prospective memory training among healthy older adults.DesignThis study was a two-arm within-participants trial with 4- and 12-wk follow-ups. Allocation ratio was 1:1, and pretraining and posttraining measurements were included. A total number of 25 healthy older adults were enrolled (mean = 63.32, SD = 4.44). Participants were randomly allocated into two conditions: (a) prospective memory training: participants underwent a multicomponent prospective memory training, and (b) control: participants were not contacted during the training phase. After the training phase was finished, participants crossed over to undergo the condition they did not experience before. The differences between pretraining and posttraining measures of prospective memory, activities of daily living, negative mood (depression), and anxiety were assessed. All changes in the measurements were analyzed using general linear method. This trial is registered at https://www.isrctn.com (#ISRCTN57600070).ResultsMulticomponent prospective memory training program was significantly effective on both subjective and objective prospective memory performances among healthy older adults. Moreover, the training had significant positive effects on activities of daily living (independence) among participants. In addition, negative mood and anxiety levels were reduced after the training was finished.ConclusionsThis multicomponent prospective memory training improved prospective memory performance and activities of daily living and reduce negative mood (depression) and anxiety levels among healthy older adults.
Brain–Heart Pathways to Blood Pressure-Related Hypoalgesia
Authors: Ottaviani Cristina , Fagioli Sabrina , Mattei Eugenio , Censi Federica , Edwards Louisa , Macaluso Emiliano , Bozzali Marco , Critchley Hugo D. , Calcagnini Giovanni 
Published: March 2018

ABSTRACT

Objective
High blood pressure (BP) is associated with reduced pain sensitivity, known as BP-related hypoalgesia. The underlying neural mechanisms remain uncertain, yet arterial baroreceptor signaling, occurring at cardiac systole, is implicated. We examined normotensives using functional neuroimaging and pain stimulation during distinct phases of the cardiac cycle to test the hypothesized neural mediation of baroreceptor-induced attenuation of pain.

Methods
Eighteen participants (10 women; 32.7 (6.5) years) underwent BP monitoring for 1 week at home, and individual pain thresholds were determined in the laboratory. Subsequently, participants were administered unpredictable painful and nonpainful electrocutaneous shocks (stimulus type), timed to occur either at systole or at diastole (cardiac phase) in an event-related design. After each trial, participants evaluated their subjective experience.

Results
Subjective pain was lower for painful stimuli administered at systole compared with diastole, F(1, 2283) = 4.82, p = 0.03. Individuals with higher baseline BP demonstrated overall lower pain perception, F(1, 2164) = 10.47, p < .0001. Within the brain, painful stimulation activated somatosensory areas, prefrontal cortex, cingulate cortex, posterior insula, amygdala, and the thalamus. Stimuli delivered during systole (concurrent with baroreceptor discharge) activated areas associated with heightened parasympathetic drive. No stimulus type by cardiac phase interaction emerged except for a small cluster located in the right parietal cortex.

Conclusions
We confirm the negative associations between BP and pain, highlighting the antinociceptive impact of baroreceptor discharge. Neural substrates associated with baroreceptor/BP-related hypoalgesia include superior parietal lobule, precentral, and lingual gyrus, regions typically involved in the cognitive aspects of pain experience.
IDO1 Expression Is Associated With Immune Tolerance and Poor Prognosis in Patients With Surgically Resected Esophageal Cancer
Authors: Kiyozumi Yuki , Baba Yoshifumi , Okadome Kazuo , Yagi Taisuke , Ishimoto Takatsugu , Iwatsuki Masaaki , Miyamoto Yuji , Yoshida Naoya , Watanabe Masayuki , Komohara Yoshihiro , Baba Hideo 
Published: March 2018

Objectives:
To evaluate the relationship between indoleamine 2, 3-dioxygenase (IDO1) expression and tumoral immune status and clinical outcome in esophageal cancer.

Summary Background Data:
IDO1 is a primary enzyme that generates immunosuppressive metabolites such as tryptophan and kynurenine. Like the PD-1/PD-L1 pathway, IDO1 plays a major role in tumor immunology and is a potential immune-based therapeutic target.

Methods:
The expressions of IDO1, CD8 (a marker of cytotoxic T cells), FOXP3 [a marker of regulatory T cells (Treg)], and PD-L1 in 305 curatively resected esophageal cancers were evaluated by immunostaining.

Results:
Overall survival was significantly better in the IDO1 negative cases (n = 234) than in the IDO1 positive cases (n = 71) [log-rank P = 0.0041; hazard ratio (HR): 1.75; 95% confidence interval (CI): 1.12–2.67; P = 0.015]. CD8 high expression was significantly positively correlated with overall survival (log-rank P = 0.025) and low IDO1 expression (P = 0.044). The inverse correlation between CD8 and IDO1 expressions was confirmed by double immunostaining for IDO1 and CD8. Stratification based on IDO1 and CD8 expressions was also significantly associated with overall survival (log-rank P = 0.0024). In addition, the IDO1-positive group was correlated with high counts of FOXP3-positive cells (P = 0.020), but not with PD-L1 expression status (P = 0.19).

Conclusions:
IDO1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. Combining the IDO1 and CD8 statuses enabled further classification of the clinical outcomes of patients.
Inference of Species Phylogenies from Bi-allelic Markers Using Pseudo-likelihood
Authors: Zhu Jiafan , Nakhleh Luay 
Published: March 2018

AbstractMotivationPhylogenetic networks represent reticulate evolutionary histories. Statistical methods for their inference under the multispecies coalescent have recently been developed. A particularly powerful approach uses data that consist of bi-allelic markers (e.g., single nucleotide polymorphism data) and allows for exact likelihood computations of phylogenetic networks while numerically integrating over all possible gene trees per marker. While the approach has good accuracy in terms of estimating the network and its parameters, likelihood computations remain a major computational bottleneck and limit the method’s applicability.ResultsIn this paper, we first demonstrate why likelihood computations of networks take orders of magnitude more time when compared to trees. We then propose an approach for inference of phylo-genetic networks based on pseudo-likelihood using bi-allelic markers. We demonstrate the scalability and accuracy of phylogenetic network inference via pseudo-likelihood computations on simulated data. Furthermore, we demonstrate aspects of robustness of the method to violations in the underlying assumptions of the employed statistical model. Finally, we demonstrate the application of the method to biological data. The proposed method allows for analyzing larger data sets in terms of the numbers of taxa and reticulation events. While pseudo-likelihood had been proposed before for data consisting of gene trees, the work here uses sequence data directly, offering several advantages as we discuss.AvailabilityThe methods have been implemented in PhyloNet (http://bioinfocs.rice.edu/phylonet).Contactjiafan.zhu@rice.edu,nakhleh@rice.edu
Profiling copy number alterations in cell-free tumour DNA using a single-reference
Authors: Robertson Alan J , Xu Qinying , Song Sarah , Ganesamoorthy Devika , Benson Derek , Chen Wenhan , Ferguson Kaltin , Nones Katia , Lakhani Sunil R , Simpson Peter T , Waddell Nicola , Pearson John V , Coin Lachlan J.M. 
Published: March 2018

AbstractBackgroundThe accurate detection of copy number alterations from the analysis of circulating cell free tumour DNA (ctDNA) in blood is essential to realising the potential of liquid biopsies. However, currently available approaches require a large number of plasma samples from healthy individuals, sequenced using the same platform and protocols to act as a reference panel. Obtaining this reference panel can be challenging, prohibitively expensive and limits the ability to migrate to improved sequencing platforms and improved protocols.MethodsWe developed qCNV and sCNA-seq, two distinct tools that together provide a new approach for profiling somatic copy number alterations (sCNA) through the analysis of cell free DNA (cfDNA) without a reference panel. Our approach was designed to identify sCNA from cfDNA through the analysis of a single plasma sample and a matched normal DNA sample -both of which can be obtained from the same blood draw. qCNV is an efficient method for extracting read-depth from BAM files and sCNA-seq is a method that uses a probabilistic model of read depth to infer the copy number segmentation of the tumour. We compared the results from our pipeline to the established copy number profile of a cell-line, as well as the results from the plasma-Seq analysis of cfDNA-like mixtures and real, clinical data-sets.ResultsWith a single, unmatched, germline reference sample, our pipeline recapitulated the known copy number profile of a cell-line and demonstrated similar results to those obtained from plasma-Seq. With less than 1X genome coverage, our approach identified clinically relevant sCNA in samples with as little as 20 % tumour DNA. When applied to plasma samples from cancer patients, our pipeline identified clinically significant mutations.ConclusionsThese results show it is possible to identify therapeutically-relevant copy number mutations from plasma samples without the need to generate a reference panel from a large number of healthy individuals. Together with the range of sequencing platforms supported by our qCNV+sCNA-Seq pipeline, as well as the Galaxy implementation of this solution, this pipeline makes cfDNA profiling more accessible and makes it easier to identify sCNA from the plasma of cancer patients.
Dissociable Roles for Working Memory in Sensorimotor Learning
Authors: McDougle Samuel D. , Taylor Jordan A. 
Published: March 2018

ABSTRACTThe computations underlying cognitive strategies in sensorimotor learning are poorly understood. Here we investigate such strategies in a sensorimotor transformation task. We show that strategies assume two forms, reflecting distinct working memory representations: discrete response caching of stimulus-response contingencies (e.g., look-up table; RC), and time-consuming parametric computations (e.g. mental rotation; MR). Subjects’ reaction times and errors suggest that both strategies are employed during learning, and trade off based on the progress of learning and the complexity of the task. Experiments using pressured preparation time support these working memory mechanisms: In discrete RC, time pressure elicits bimodal distributions of movements, in agreement with cached responses; in parametric MR, time pressure elicits a shifting distribution producing intermediate movements between visual targets and distal goals, consistent with analog re-computing of a movement plan. These results provide a specific model of working memory contributions to motor learning.
Host Diet Influences Lethal and Sublethal Responses of Hosts to Amphibian Pathogen Exposure
Authors: Rumschlag Samantha L. , Boone Michelle D. 
Published: March 2018

AbstractThe severity of the impacts of pathogens on hosts may be driven by environmental factors like resource availability that create tradeoffs on energetic demands for immune responses and basal metabolic activity within the host. These responses can vary among species from sublethal to lethal effects, which can have consequences for the host population trajectories within a community. Chytridiomycosis, caused by the pathogen Batrachochytrium dendrobatidis (or Bd), has been associated with global amphibian population declines. However, it also occurs in populations without appearing to cause mass mortality; the effect of Bd in these situations is not well understood and environmental factors like food abundance that impact host conditions could play an important role in the magnitude of the pathogen’s impact. In the present study, we exposed American toad (Anaxyrus americanus), northern leopard frog (Lithobates pipiens), and Blanchard’s cricket frog (Acris blanchardi) metamorphs to Bd and then reared them in the terrestrial habitat under low or high food environments. We found additive effects of Bd and reduced food abundance on host growth and survival that varied according to species. For instance, Bd-induced reductions in American toad survival were greater under low food conditions compared to high food conditions but survival of northern leopard frogs and Blanchard’s cricket frogs was not affected by Bd. For northern leopard frogs and Blanchard’s cricket frogs, low food abundance resulted in the lower growth rates under Bd exposure compared to high food abundance. Additionally, we developed stage-structured population models for American toads to assess if reduced survival of metamorphs exposed to Bd under conditions of low and high food abundance could influence population trajectories; models indicated that Bd exposure would reduce annual population growth rates by 14% under conditions of high food abundance and 21% under conditions of low food abundance. Our results suggest that environmental conditions that influence resource availability for species that are sensitive or tolerant to Bd may increase the negative effects of Bd on host growth and survival, which could have important implications for how populations and communities with infected members respond over time.