bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Variation in SLC8A1 Gene Involved in Blood Pressure Responses to Acute Salt Loading
Authors: Liu Kuo , Liu Zheng , Qi Han , Liu Bin , Wu Jingjing , Liu Yezhou , Zhang Jie , Cao Han , Yan Yuxiang , He Yan , Zhang Ling 
Published: November 2017

AbstractBACKGROUNDSalt sensitivity of blood pressure (SSBP) increases the risk of cardiovascular complications, and the heritability of SSBP is about 50% in Chinese population. However, studies identifying genes involved in BP responses to acute sodium loading and diuresis shrinkage are still limited.METHODA total of 342 essential hypertensives from Beijing were recruited in our study. A modified Sullivan’s acute oral saline load and diuresis shrinkage test was conducted to each individual. Medical history and lifestyle risk factors were obtained by questionnaire. Generalized linear model was used to examine the associations of 29 single-nucleotide polymorphisms (SNPs) with SSBP and false discovery rate (FDR) was used to correct P values for multiple testing.RESULTSIn the process of acute sodium loading, after adjusting for age and 24-hour urinary sodium concentration, SNPs in CYP11B2, PRKG1, SLC8A1 genes were significantly associated with systolic BP (SBP) rising in the additive and recessive model; SNPs in CYP4A11, PRKG1, SLC8A1, and ADRB2 genes were significantly associated with diastolic BP (DBP) rising. In the process of diuresis shrinkage, SNPs of CLCNKA, eNOS, PRKG1 gene were associated with SBP and DBP decreasing. After FDR correction, rs434082 in SLC8A1 gene was still significantly associated with blood pressure rising during salt load. In the additive model, A allele increased DBP of 2.8 mm Hg (FDR_q = 0.029) and MAP of 3.1 mm Hg (FDR_q = 0.029) after adjusting for age and 24-hour urinary sodium concentration.CONCLUSIONSLC8A1 gene may contribute to BP change in the process of acute sodium loading in a Han Chinese population.
The Impact of Intradialytic Pedaling Exercise on Arterial Stiffness: A Pilot Randomized Controlled Trial in a Hemodialysis Population
Authors: Cooke Alexandra B , Ta Vincent , Iqbal Sameena , Gomez Yessica-Haydee , Mavrakanas Thomas , Barré Paul , Vasilevsky Murray , Rahme Elham , Daskalopoulou Stella S 
Published: November 2017

Abstract

OBJECTIVES
Regular exercise is known to reduce arterial stiffness (AS) in hemodialysis patients. However, the impact of a more realistic intradialytic form of exercise, such as pedaling, is unclear. We aimed to examine (i) the effect of intradialytic pedaling exercise on AS over 4 months and (ii) the longer term effect of pedaling on AS 4 months after exercise cessation.

METHODS
Patients on stable in-center hemodialysis (3 x/week) were randomly assigned 1:1 to either intradialytic pedaling exercise (EX) or to a control group receiving usual hemodialysis (nonEX) for 4 months. At baseline and 4 months, peripheral and central blood pressure (BP) indices, heart rate (HR), augmentation index HR corrected (AIx75), and carotid-femoral pulse wave velocity (cfPWV) were assessed (applanation tonometry). Measurements were repeated in the EX group 4 months postexercise cessation.

RESULTS
As per protocol analysis was completed in 10 EX group participants (58 ± 17 years, body mass index 26 ± 4 kg/m2) and 10 nonEX group participants (53 ± 15 years, body mass index 27 ± 6 kg/m2). Peripheral and central BP was unchanged in both groups. AIx75 was unchanged in the EX group, however, a significant median increase of 3.5% [interquartile range, IQR 1.0, 8.5] was noted in the nonEX group (P = 0.009). We noted a significantly greater absolute decrease in cfPWV in the EX group compared to controls: −1.00 [IQR −1.95, 0.05] vs. 0.20 [IQR −0.10, 0.90] (P = 0.033). Interestingly, the decrease in cfPWV observed in the EX group was partially reversed 4 months after exercise cessation.

CONCLUSION
Intradialytic pedaling exercise has a beneficial impact on AS. This relationship warrants further investigation.

CLINICAL TRIALS REGISTRATION
Trial Number #NCT03027778 (clinicaltrials.gov)
TabPath: interactive tables for metabolic pathway analysis
Authors: Moraes Lauro Ângelo Gonçalves de , Felestrino Érica Barbosa , Assis Renata de Almeida Barbosa , Matos Diogo , Lima Joubert de Castro , Lima Leandro de Araújo , Almeida Nalvo Franco , Setubal João Carlos , Garcia Camila Carrião Machado , Moreira Leandro Marcio 
Published: November 2017

Abstract

Motivation
Information about metabolic pathways in a comparative context is one of the most powerful tool to help the understanding of genome-based differences in phenotypes among organisms. Although several platforms exist that provide a wealth of information on metabolic pathways of diverse organisms, the comparison among organisms using metabolic pathways is still a difficult task.

Results
We present TabPath (Tables for Metabolic Pathway), a web-based tool to facilitate comparison of metabolic pathways in genomes based on KEGG. From a selection of pathways and genomes of interest on the menu, TabPath generates user-friendly tables that facilitate analysis of variations in metabolism among the selected organisms.

Availability and implementation
TabPath is available at http://200.239.132.160:8686.
Human Cortical Thickness Organized into Genetically-determined Communities across Spatial Resolutions
Authors: Alexander-Bloch Aaron F , Mathias Samuel R , Fox Peter T , Olvera Rene L , Göring Harold H H , Duggirala Ravi , Curran Joanne E , Blangero John , Glahn David C 
Published: November 2017

AbstractThe cerebral cortex may be organized into anatomical genetic modules, communities of brain regions with shared genetic influences via pleiotropy. Such modules could represent novel phenotypes amenable to large-scale gene discovery. This modular structure was investigated with network analysis of in vivo MRI of extended pedigrees, revealing a “multiscale” structure where smaller and larger modules exist simultaneously and in partially overlapping fashion across spatial scales, in contrast to prior work suggesting a specific number of cortical thickness modules. Inter-regional genetic correlations, gene co-expression patterns and computational models indicate that two simple organizational principles account for a large proportion of the apparent complexity in the network of genetic correlations. First, regions are strongly genetically correlated with their homologs in the opposite cerebral hemisphere. Second, regions are strongly genetically correlated with nearby regions in the same hemisphere, with an initial steep decrease in genetic correlation with anatomical distance, followed by a more gradual decline. Understanding underlying organizational principles of genetic influence is a critical step towards a mechanistic model of how specific genes influence brain anatomy and mediate neuropsychiatric risk.
Gaussian approximation of general non-parametric posterior distributions
Authors: Shang Zuofeng , Cheng Guang 
Published: November 2017

AbstractIn a general class of Bayesian non-parametric models, we prove that the posterior distribution can be asymptotically approximated by a Gaussian process (GP). Our results apply to non-parametric exponential family that contains both Gaussian and non-Gaussian regression and also hold for both efficient (root-$n$) and inefficient (non-root-$n$) estimations. Our general approximation theorem does not rely on posterior conjugacy and can be verified in a class of GP priors that has a smoothing spline interpretation. In particular, the limiting posterior measure becomes prior free under a Bayesian version of ‘under-smoothing’ condition. Finally, we apply our approximation theorem to examine the asymptotic frequentist properties of Bayesian procedures such as credible regions and credible intervals.
Equivariant Morse Theory for the Norm-Square of a Moment Map on a Variety
Authors: Wilkin Graeme 
Published: November 2017

AbstractWe show that the main theorem of Morse theory holds for a large class of functions on singular spaces. The function must satisfy certain conditions extending the usual requirements on a manifold that Condition C holds and the gradient flow around the critical sets is well-behaved, and the singular space must satisfy a local deformation retract condition. We then show that these conditions are satisfied when the function is the norm-square of a moment map on an affine variety, and that the homotopy equivalence from this theorem is equivariant with respect to the associated Hamiltonian group action. An important special case of these results is that the main theorem of Morse theory holds for the norm square of a moment map on the space of representations of a finite quiver with relations.
Compliance with patient-reported outcome assessment in glioma patients: predictors for drop out
Authors: Renovanz Mirjam , Hechtner Marlene , Kohlmann Karoline , Janko Mareile , Nadji-Ohl Minou , Singer Susanne , Ringel Florian , Coburger Jan , Hickmann Anne-Katrin 
Published: November 2017

Abstract

Background
Patient-reported outcomes are of high importance in clinical neuro-oncology. However, assessment is still suboptimal. We aimed at exploring factors associated with the probability for a) drop out of study and b) death during follow-up.

Methods
Patients were assessed twice during follow-up visits scheduled within 3 to 5 months of each other by using 3 validated patient-reported outcome measures (t1: first assessment, t2: second assessment). As “death” was seen as a competing risk for drop out, univariate competing risk Cox regression models were applied to explore factors associated with dropping out (age, gender, WHO grade, living situation, recurrent surgery, Karnofsky Performance Status, time since diagnosis, and patient-reported outcomes assessed by Distress Thermometer, EORTC-QLQ-C30, EORTC-QLQ-BN20, and SCNS-SF-34G).

Results
Two hundred forty-six patients were eligible, 173 (70%) participated. Patients declining participation were diagnosed with glioblastomas more often than with other gliomas (56% vs 39%). At t2, 32 (18%) patients dropped out, n = 14 death-related, n = 18 for other reasons. Motor dysfunction (EORTC-QLQ-BN20) was associated with higher risk for non-death-related drop out (HR: 1.02; 95% CI, 1.00–1.03; P = .03). Death-related drop out was associated with age (HR: 1.09; 95% CI, 1.03–1.14; P = .002), Karnofsky Performance Status (HR: 0.92; 95% CI, 0.88–0.96; P < .001), lower physical functioning (EORTC-QLQ-C30; HR: 0.98; 95% CI, 0.96–1.00; P = .04) and lower motor functioning (EORTC-QLQ-BN20; HR: 1.020; 95% CI, 1.00–1.04; P = .02).

Conclusion
Patients with motor dysfunction and poorer clinical condition seem to be more likely to drop out of studies applying patient-reported outcome measures. This should be taken into account when planning studies assessing glioma patients and for interpretation of results of patient-reported outcome assessments in clinical routine.
Emergence of Resistance Mutations in Salmonella enterica Serovar Typhi Against Fluoroquinolones
Authors: Matono Takashi , Morita Masatomo , Yahara Koji , Lee Ken-ichi , Izumiya Hidemasa , Kaku Mitsuo , Ohnishi Makoto 
Published: November 2017

Abstract

Background
Little is known about the evolutionary process and emergence time of resistance mutations to fluoroquinolone in Salmonella enterica serovar Typhi.

Methods
We analyzed S. Typhi isolates collected from returned travelers between 2001 and 2016. Based on ciprofloxacin susceptibility, isolates were categorized as highly resistant (minimum inhibitory concentration [MIC] ≥ 4 μg/mL [CIPHR]), resistant (MIC = 1–2 μg/mL [CIPR]), intermediate susceptible (MIC = 0.12–0.5 μg/mL [CIPI]), and susceptible (MIC ≤ 0.06 μg/mL [CIPS]).

Results
A total of 107 isolates (33 CIPHR, 14 CIPR, 30 CIPI, and 30 CIPS) were analyzed by whole-genome sequencing; 2461 single nucleotide polymorphisms (SNPs) were identified. CIPS had no mutations in the gyrA or parC genes, while each CIPI had 1 of 3 single mutations in gyrA (encoding Ser83Phe [63.3%], Ser83Tyr [33.3%], or Asp87Asn [3.3%]). CIPHR had the same 3 mutations: 2 SNPs in gyrA (encoding Ser83Phe and Asp87Asn) and a third in parC (encoding Ser80Ile). CIPHR shared a common ancestor with CIPR and CIPI isolates harboring a single mutation in gyrA encoding Ser83Phe, suggesting that CIPHR emerged 16 to 23 years ago.

Conclusions
Three SNPs—2 in gyrA and 1 in parC—are present in S. Typhi strains highly resistant to fluoroquinolone, which were found to have evolved in 1993–2000, approximately 10 years after the beginning of the ciprofloxacin era. Highly resistant strains with survival advantages arose from strains harboring a single mutation in gyrA encoding Ser83Phe. Judicious use of fluoroquinolones is warranted to prevent acceleration of such resistance mechanisms in the future.
Implication of First-Line Antiretroviral Therapy Choice on Second-Line Options
Authors: Meloni Seema T , Onwuamah Chika K , Agbaji Oche , Chaplin Beth , Olaleye David O , Audu Rosemary , Samuels Jay , Ezechi Oliver , Imade Godwin , Musa Adesola Z , Odaibo Georgina , Okpokwu Jonathan , Rawizza Holly , Mu’azu Muhammad A , Dalhatu Ibrahim , Ahmed Mukhtar , Okonkwo Prosper , Raizes Elliot , Ujah Innocent A O , Yang Chunfu , Idigbe Emmanuel O , Kanki Phyllis J 
Published: November 2017

AbstractBackgroundAlthough there are a number of studies comparing the currently recommended preferred and alternative first-line (1L) antiretroviral therapy (ART) regimens on clinical outcomes, there are limited data examining the impact of 1L regimen choice and duration of virologic failure (VF) on accumulation of drug resistance mutations (DRM). The patterns of DRM from patients failing zidovudine (AZT)-containing versus tenofovir (TDF)-containing ART were assessed to evaluate the predicted susceptibility to second-line (2L) nucleoside reverse-transcriptase inhibitor (NRTI) backbone options in the context of an ongoing programmatic setting that uses viral load (VL) monitoring.MethodsPaired samples from Nigerian ART patients who experienced VF and switched to 2L ART were retrospectively identified. For each sample, the human immunodeficiency virus (HIV)-1 polymerase gene was sequenced at 2 time points, and DRM was analyzed using Stanford University’s HIVdb program.ResultsSequences were generated for 191 patients. At time of 2L switch, 28.2% of patients on AZT-containing regimens developed resistance to TDF, whereas only 6.8% of patients on TDF-containing 1L had mutations compromising susceptibility to AZT. In a stratified evaluation, patients with 0–6 months between tested VL samples had no difference in proportion compromised to 2L, whereas those with &gt;6 months between samples had a statistically significant difference in proportion with compromised 2L NRTI. In multivariate analyses, patients on 1L AZT had 9.90 times higher odds of having a compromised 2L NRTI option than patients on 1L TDF.ConclusionsIn the context of constrained resources, where VL monitoring is limited, we present further evidence to support use of TDF as the preferred 1L NRTI because it allows for preservation of the recommended 2L NRTI option.
Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα
Authors: Krumm Elizabeth A , Patel Vipa J , Tillery Taylor S , Yasrebi Ali , Shen Jianliang , Guo Grace L , Marco Stephanie M , Buckley Brian T , Roepke Troy A 
Published: November 2017

Abstract
Flame retardants (FRs) such as polybrominated diphenyl ethers and organophosphate FR (OPFR) persist in the environment and interact with multiple nuclear receptors involved in homeostasis, including estrogen receptors (ERs). However, little is known about the effects of FR, especially OPFR, on mammalian neuroendocrine functions. Therefore, we investigated if exposure to FR alters hypothalamic gene expression and whole-animal physiology in adult wild-type (WT) and ERα KO mice. Intact WT and KO males and ovariectomized WT and KO females were orally dosed daily with vehicle (oil), 17α-ethynylestradiol (2.5 μg/kg), 2,2’, 4,4-tetrabromodiphenyl ether (BDE-47, 1 or 10 mg/kg), or an OPFR mixture {1 or 10 mg/kg of tris(1, 3-dichloro-2-propyl)phosphate, triphenyl phosphate, and tricresyl phosphate each} for 28 days. Body weight, food intake, body composition, glucose and insulin tolerance, plasma hormone levels, and hypothalamic and liver gene expression were measured. Expression of neuropeptides, receptors, and cation channels was differentially altered between WT males and females. OPFR suppressed body weight and energy intake in males. FR increased fasting glucose levels in males, and BDE-47 augmented glucose clearance in females. Liver gene expression indicated FXR activation by BDE-47 and PXR and CAR activation by OPFR. In males, OPFR increased ghrelin but decreased leptin and insulin independent of body weight. The loss of ERα reduced the effects of both FR on hypothalamic and liver gene expression and plasma hormone levels. The physiological implications are that males are more sensitive than ovariectomized females to OPFR exposure and that these effects are mediated, in part, by ERα.
Predictors of Intubation in Patients With Acute Hypoxemic Respiratory Failure Treated With a Noninvasive Oxygenation Strategy*
Authors: Frat Jean-Pierre , Ragot Stéphanie , Coudroy Rémi , Constantin Jean-Michel , Girault Christophe , Prat Gwénael , Boulain Thierry , Demoule Alexandre , Ricard Jean-Damien , Razazi Keyvan , Lascarrou Jean-Baptiste , Devaquet Jérôme , Mira Jean-Paul , Argaud Laurent , Chakarian Jean-Charles , Fartoukh Muriel , Nseir Saad , Mercat Alain , Brochard Laurent , Robert René , Thille Arnaud W. 
Published: November 2017

Objectives:
In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques.

Design:
Post hoc analysis of a randomized clinical trial.

Setting:
Twenty-three ICUs.

Patients:
Patients with a respiratory rate greater than 25 breaths/min and a Pao
2/Fio
2 ratio less than or equal to 300 mm Hg.

Intervention:
Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation.

Measurement and Main Results:
Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13–6.75; p = 0.03). One hour after high-flow nasal cannula oxygen initiation, increased heart rate was the only factor associated with intubation. One hour after noninvasive ventilation initiation, a Pao
2/Fio
2 ratio less than or equal to 200 mm Hg and a tidal volume greater than 9 mL/kg of predicted body weight were independent predictors of intubation (adjusted odds ratio, 4.26; 95% CI, 1.62–11.16; p = 0.003 and adjusted odds ratio, 3.14; 95% CI, 1.22–8.06; p = 0.02, respectively). A tidal volume above 9 mL/kg during noninvasive ventilation remained independently associated with 90-day mortality.

Conclusions:
In patients with acute hypoxemic respiratory failure breathing spontaneously, the respiratory rate was a predictor of intubation under standard oxygen, but not under high-flow nasal cannula oxygen or noninvasive ventilation. A Pao
2/Fio
2 below 200 mm Hg and a high tidal volume greater than 9 mL/kg were the two strong predictors of intubation under noninvasive ventilation.
Finding domain-general metacognitive mechanisms requires using appropriate tasks
Authors: Ruby Eugene , Giles Nathan , Lau Hakwan 
Published: November 2017

AbstractAn important yet unresolved question is whether or not metacognition consists of domain-general or domain-specific mechanisms. While most studies on this topic suggest a dissociation between metacognitive abilities at the neural level, there are conflicting reports at the behavioral level. Specifically, while McCurdy et al. (2013) found a positive correlation between metacognitive efficiency for visual perception and memory, Baird et al. (2013) didn’t find this correlation. One possible explanation for this disparity is that the former included two-alternative-forced choice (2AFC) judgments in both their visual and memory tasks, whereas the latter used 2AFC for one task and yes/no (YN) judgments for the other. In support of this hypothesis, we ran two online experiments meant to mirror McCurdy et al. (2013) and Baird et al. (2013) with considerable statistical power (n=100), and replicated the main findings of both studies. This suggests the finding of McCurdy et al (2013) was not a ‘fluke’ (i.e. false positive). In a third experiment with the same sample size, which included YN judgments for both tasks, we did not find a correlation between metacognitive functions, suggesting that the conflict between McCurdy et al. (2013) and Baird et al. (2013) stemmed from the use of YN judgments in the latter study. Our results underscore the need to avoid conflating 2AFC and YN judgments, which is a common problem.
Axons from the Trigeminal Ganglia are the Earliest Afferent Projections to the Mouse Cerebellum
Authors: Marzban Hassan , Rahimi-Balaei Maryam , Hawkes Richard 
Published: November 2017

ABSTRACTThe first stage standard model for the development of afferent pathways to the cerebellum is that ingrowing axons target the embryonic Purkinje cells (E13-E16 in mice). Perinatally and early postnatal (E18-P15) the climbing fibers translocate to the Purkinje cell dendrites, and as the granular layer develops the mossy fibers translocate from the Purkinje cell somata and synapse with granule cell dendrites. In this report we describe a novel earlier stage in the development. Immunostaining for a neurofilament-associated antigen (NAA) reveals the early axon distributions with remarkable clarity. Axons from the trigeminal system enter the cerebellar primordium as early as embryo age (E)9. By using a combination of axon tract tracing, analysis ofneurogenin1null mice – which do not develop trigeminal ganglia – and mouse embryos maintainedin vitro– we show that the first axons to innervate the cerebellar primordium are direct projections from the trigeminal ganglia. The data show that the early trigeminal projections arein situbefore the Purkinje cells are born, and double immunostaining for NAA and markers of the different domains in the cerebellar primordium reveal that they first target the cerebellar nuclear neurons of the nuclear transitory zone (E9-E10), and only later (E10-E11) extend collateral branches to the Purkinje cell plate.