bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping genes for calcium signaling and their associated human genetic disorders
Authors: Hörtenhuber Matthias , Toledo Enrique M , Smedler Erik , Arenas Ernest , Malmersjö Seth , Louhivuori Lauri , Uhlén Per 
Published: April 2017

Abstract

Motivation
Signal transduction via calcium ions (Ca2+) represents a fundamental signaling pathway in all eukaryotic cells. A large portion of the human genome encodes proteins used to assemble signaling systems that can transduce signals with diverse spatial and temporal dynamics.

Results
Here, we provide a map of all of the genes involved in Ca2+ signaling and link these genes to human genetic disorders. Using Gene Ontology terms and genome databases, 1805 genes were identified as regulators or targets of intracellular Ca2+ signals. Associating these 1805 genes with human genetic disorders uncovered 1470 diseases with mutated ‘Ca2+ genes’. A network with scale-free properties appeared when the Ca2+ genes were mapped to their associated genetic disorders.

Availability and Implementation
The Ca2+ genome database is freely available at http://cagedb.uhlenlab.org and will foster studies of gene functions and genetic disorders associated with Ca2+ signaling.

Supplementary information
Supplementary data are available at Bioinformatics online.
Evolving Failures in the Delivery of Human Immunodeficiency Virus Care: Lessons From a Ugandan Meningitis Cohort 2006–2016
Authors: Flynn Andrew G. , Meya David B. , Hullsiek Katherine Huppler , Rhein Joshua , Williams Darlisha A. , Musubire Abdu , Morawski Bozena M. , Taseera Kabanda , Sadiq Alisat , Ndyatunga Liberica , Roediger Mollie , Rajasingham Radha , Bohjanen Paul R. , Muzoora Conrad , Boulware David R. 
Published: April 2017

Abstract

Background
Because of investments in human immunodeficiency virus (HIV) care in sub-Saharan Africa, the number of people aware of their status and receiving antiretroviral therapy (ART) has increased; however, HIV/acquired immune deficiency syndrome (AIDS) mortality still remains high.

Methods
We performed retrospective analysis of 3 sequential prospective cohorts of HIV-infected Ugandan adults presenting with AIDS and meningitis from 2006 to 2009, 2010 to 2012, and 2013 to 2016. Participants were categorized as follows: (1) unknown HIV status; (2) known HIV+ without ART; (3) known HIV+ with previous ART. We further categorized 2006 and 2013 cohort participants by duration of HIV-status knowledge and of ART receipt.

Results
We screened 1353 persons with suspected meningitis. Cryptococcus was the most common pathogen (63%). Over the decade, we observed an absolute increase of 37% in HIV status knowledge and 59% in antecedent ART receipt at screening. The 2006 cohort participants were new/recent HIV diagnoses (65%) or known HIV+ but not receiving ART (35%). Many 2013 cohort participants were new/recent HIV diagnoses (34%) and known HIV+ with &lt;1 month ART (20%), but a significant proportion were receiving ART 1–4 months (11%) and &gt;4 months (30%). Four percent of participants discontinued ART. From 2010 to 2016, meningitis cases per month increased by 33%.

Conclusions
Although improved HIV screening and ART access remain much-needed interventions in resource-limited settings, greater investment in viral suppression and opportunistic infection care among the growing HIV-infected population receiving ART is essential to reducing ongoing AIDS mortality.
GNAQ TT(-695/-694)GC Polymorphism Is Associated with Increased Gq Expression, Vascular Reactivity, and Myocardial Injury after Coronary Artery Bypass Surgery
Authors: Frey Ulrich H. , Klenke Stefanie , Mitchell Anna , Knüfermann Tim , Jakob Heinz , Thielmann Matthias , Siffert Winfried , Peters Jürgen 
Published: April 2017

Abstract

Background
Angiotensin II receptor type 1–mediated activation of the α-subunit of the heterotrimeric Gq protein evokes increased vasoconstriction and may promote hypertrophy-induced myocardial damage. The authors recently identified a TT(-695/-694)GC polymorphism in the human Gq promoter, the GC allele being associated with an increased prevalence of cardiac hypertrophy. In this article, the authors tested whether the TT(-695/-694)GC polymorphism is associated with differences in (1) myocardial Gq protein expression, (2) vascular reactivity, and (3) myocardial damage after coronary artery bypass grafting.

Methods
Gq protein expression was measured in right atrial muscle from 55 patients undergoing coronary artery bypass grafting as were skin perfusion changes (n = 18; laser Doppler imaging), saphenous vein ring vascular reactivity (n = 50, organ bath) in response to angiotensin II, and myocardial damage (227 patients undergoing coronary artery bypass grafting), as assessed by postoperative cardiac troponin I concentration.

Results
Myocardial Gq expression was greater in GC/GC genotypes (GC/GC vs. TT/TT: 1.27-fold change; P = 0.006). Skin perfusion after intradermal angiotensin II injection decreased only in GC/GC genotypes (P = 0.0002). Saphenous vein rings exposed to increasing angiotensin II concentrations showed an almost doubled maximum contraction in GC/GC compared with individuals with the TT/TT genotype (P = 0.022). In patients undergoing coronary artery bypass grafting, baseline cardiac ejection fraction was different (GC/GC: 55 ± 13%; GC/TT: 54 ± 14%; TT/TT: 48 ± 15%; P = 0.037) and postoperative peak cardiac troponin I was greater in patients with the GC/GC (11.5 ± 13.8 ng/ml) than in patients with the GC/TT (9.2 ± 9.2 ng/ml) or patients with the TT/TT genotype (6.6 ± 4.8 ng/ml, P = 0.015).

Conclusions
The GC/GC genotype of the TT(-695/-694)GC polymorphism is associated with increased Gq protein expression, augmented angiotensin II receptor type 1–related vasoconstriction, and increased myocardial injury after coronary artery bypass grafting, highlighting the impact of Gq genotype variation.
Inhibition of Metabotropic Glutamate Receptor Subtype 1 Alters the Excitability of the Commissural Pyramidal Neuron in the Rat Anterior Cingulate Cortex after Chronic Constriction Injury to the Sciatic Nerve
Authors: Gao Shi-Hao , Shen Lin-Lin , Wen Hui-Zhong , Zhao Yan-Dong , Ruan Huai-Zhen 
Published: April 2017

Abstract

Background
Inhibition of the metabotropic glutamate receptor subtype 1 in the anterior cingulate cortex has an analgesic effect during sustained nociceptive hypersensitivity. However, the specific changes in different subtypes of anterior cingulate cortex layer 5 pyramidal neurons, as well as the distinct effect of metabotropic glutamate receptor subtype 1 inhibition on different neuronal subtypes, have not been well studied.

Methods
Retrograde labeling combined with immunofluorescence, whole cell clamp recording, and behavioral tests combined with RNA interference were performed in a rat model of chronic constriction injury to the sciatic nerve.

Results
Commissural layer 5 pyramidal neurons (projecting to the contralateral cortex) existed in the anterior cingulate cortex. The voltage-gated potassium channel subunit 2–mediated current in these neurons were substantially reduced after chronic constriction injury (current densities at +30 mV for the sham, and chronic constriction injury neurons were [mean ± SD] 10.22 ± 3.42 pA/pF vs. 5.58 ± 2.71 pA/pF, respectively; n = 11; P < 0.01), which increased the spike width and fast afterhyperpolarization potential, resulting in hyperexcitability. Inhibition of metabotropic glutamate receptor subtype 1 alleviated the down-regulation of voltage-gated potassium channel subunit 2 currents (current density increased by 8.11 ± 3.22 pA/pF; n = 7; P < 0.01). Furthermore, knockdown of voltage-gated potassium channel subunit 2 current in the commissural neurons attenuated the analgesic effect of metabotropic glutamate receptor subtype 1 inhibition (n = 6 rats; P < 0.05).

Conclusions
The effect of metabotropic glutamate receptor subtype 1 inhibition on commissural anterior cingulate cortex layer 5 pyramidal neurons is likely different with the modification of previously studied hyperpolarization-activated/cyclic nucleotide-gated channel-dependent neurons but relies on the alteration of voltage-gated potassium channel subunit 2 currents. These results will contribute to a better understanding of the therapeutic role of metabotropic glutamate receptor subtype 1 in chronic pain.
Beyond cascade screening: detection of familial hypercholesterolaemia at childhood immunization and other strategies
Authors: Martin Andrew C. , Bell Damon A. , Brett Tom , Watts Gerald F. 
Published: April 2017

Purpose of review
Familial hypercholesterolaemia is a common genetic disorder that accelerates premature coronary heart disease. Although effective treatments are available, the majority of individuals remain undiagnosed. We review new evidence for improving the detection of familial hypercholesterolaemia.

Recent findings
Recent studies have demonstrated that universal screening of children for familial hypercholesterolaemia may be highly effective at the time of immunization if combined with reverse cascade testing of adult family members, who have a more immediate risk of a coronary event. Alerts on laboratory reports and the application of bioinformatics to electronic health records may also be useful for identifying familial hypercholesterolaemia in community settings. Effective detection, diagnosis, and codification of familial hypercholesterolaemia are essential for the development of registries.

Summary
Although the cost-effectiveness of screening programs for familial hypercholesterolaemia in childhood remains to be established, combining universal and reverse cascade screening, complemented by opportunistic identification of individuals in high-risk settings, use of laboratory alerts, and screening of electronic health records are likely to have a high yield in the detection of familial hypercholesterolaemia in the community.
Interrater and Test-Retest Reliability of the Beery Visual-Motor Integration in Schoolchildren
Authors: Harvey Erin M. , Leonard-Green Tina K. , Mohan Kathleen M. , Kulp Marjean Taylor , Davis Amy L. , Miller Joseph M. , Twelker J. Daniel , Campus Irene , Dennis Leslie K. 
Published: April 2017

ABSTRACT

Purpose
To assess interrater and test-retest reliability of the 6th Edition Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI) and test-retest reliability of the VMI Visual Perception Supplemental Test (VMIp) in school-age children.

Methods
Subjects were 163 Native American third- to eighth-grade students with no significant refractive error (astigmatism <1.00 D, myopia <0.75 D, hyperopia <2.50 D, anisometropia <1.50 D) or ocular abnormalities. The VMI and VMIp were administered twice, on separate days. All VMI tests were scored by two trained scorers, and a subset of 50 tests was also scored by an experienced scorer. Scorers strictly applied objective scoring criteria. Analyses included interrater and test-retest assessments of bias, 95% limits of agreement, and intraclass correlation analysis.

Results
Trained scorers had no significant scoring bias compared with the experienced scorer. One of the two trained scorers tended to provide higher scores than the other (mean difference in standardized scores = 1.54). Interrater correlations were strong (0.75 to 0.88). VMI and VMIp test-retest comparisons indicated no significant bias (subjects did not tend to score better on retest). Test-retest correlations were moderate (0.54 to 0.58). The 95% limits of agreement for the VMI were −24.14 to 24.67 (scorer 1) and −26.06 to 26.58 (scorer 2), and the 95% limits of agreement for the VMIp were −27.11 to 27.34.

Conclusions
The 95% limit of agreement for test-retest differences will be useful for determining if the VMI and VMIp have sufficient sensitivity for detecting change with treatment in both clinical and research settings. Further research on test-retest reliability reporting 95% limits of agreement for children across different age ranges is recommended, particularly if the test is to be used to detect changes due to intervention or treatment.
Improvement of Image Quality in Unenhanced Dual-Layer CT of the Head Using Virtual Monoenergetic Images Compared With Polyenergetic Single-Energy CT
Authors: Neuhaus Victor , Abdullayev Nuran , Große Hokamp Nils , Pahn Gregor , Kabbasch Christoph , Mpotsaris Anastasios , Maintz David , Borggrefe Jan 
Published: April 2017

Objectives
The aims of this study were to compare virtual monoenergetic images and polyenergetic images reconstructed from unenhanced dual-layer detector computed tomography (DLCT) of the head and to determine kiloelectron volt levels that optimize image quality, particularly the gray-white matter contrast, and reduce beam hardening artifacts caused by the skull.

Materials and Methods
Institutional review board approval was obtained. Forty patients that received DLCT were included in this retrospective study; of these patients, 22 were women and 18 were men. The average age was 61.5 ± 14.3 years. Virtual monoenergetic images were reconstructed from spectral base images at 40 keV to 120 keV. To calculate signal-to-noise ratio and contrast-to-noise ratio, attenuation and standard deviation of supratentorial gray and white matter were measured in virtual monoenergetic and polyenergetic images. Beam hardening artifacts were detected close to the calvarium and in the posterior fossa. Two radiologists rated the assessment of gray-white matter differentiation and of the subcalvarial space, as well as the artifacts caused by the skull and image noise. Student t test and Wilcoxon test were used to determine significance.

Results
Compared with polyenergetic images, superior signal-to-noise ratio and superior contrast-to-noise ratio of gray and white matter were observed in virtual monoenergetic images at low kiloelectron volt levels (P < 0.0001). Subcalvarial artifacts were significantly lower at 120 keV (P < 0.02). Artifacts measured in the posterior fossa were generally lower at high kiloelectron volt levels; however, no statistical significance was detected. Virtual monoenergetic images were rated superior to polyenergetic images in regard to all 4 criteria (P < 0.0001). The observers reported an optimal radiological assessment of gray-white matter differentiation at 65 keV and optimal assessment of subcalvarial space at 120 keV.

Conclusions
In comparison to polyenergetic images, virtual monoenergetic images reconstructed from unenhanced DLCT of the head at 65 keV and 120 keV allow to optimize gray-white matter contrast and reduce beam hardening artifacts caused by the skull, respectively.
Clinical Robustness of Accelerated and Optimized Abdominal Diffusion-Weighted Imaging
Authors: Taron Jana , Weiß Jakob , Martirosian Petros , Seith Ferdinand , Stemmer Alto , Bamberg Fabian , Notohamiprodjo Mike 
Published: April 2017

Objectives
The aim of this study was to assess the robustness of an accelerated and optimized diffusion-weighted sequence in clinical routine abdominal imaging using the simultaneous multislice (SMS) technique for scan time reduction and 3-dimensional (3D) diagonal diffusion mode to optimize image quality.

Materials and Methods
One hundred fifty consecutive patients received clinically indicated magnetic resonance imaging for abdominal imaging including an optimized SMS diffusion-weighted sequence (DWIOPT: diffusion mode 3D diagonal; SMS factor 2; scan time 1:44 minutes). A subgroup of 41 patients additionally received a standard diffusion-weighted sequence as reference (DWISTD: diffusion mode 4-scan trace; scan time 2:35 minutes). Qualitative and quantitative image parameters of DWISTD and DWIOPT were assessed and compared interindividually within the subgroup using dedicated statistics.

Results
In all patients, image quality ratings in DWIOPT were rated very high (overall image quality, 4.6 [4–5]; contour sharpness of right/left hepatic lobe, 4.6 [4–5]/4.4 [4–5]; and lesion conspicuity, 4.5 [4.5–5]). Interindividually, DWIOPT proved superior to DWISTD in comparison of overall image quality (4.6 [4.6–4.7] vs 4.2 [4.1–4.2]; P = 0.025) and contour sharpness of the right/left hepatic lobe (4.6 [4.5–4.7]/4.3 [4.0–4.3] vs 4.3 [4.1–43]/4.0[3.0–4.0]; each P = 0.045); lesion conspicuity was comparable in DWIOPT and DWISTD (4.0 [4.8–5] vs 4.4 [4–5]; P = 0.461), and apparent diffusion coefficient (ADC) values showed no statistically significant difference (ADCOPT vs ADCSTD: right hepatic lobe, P = 0.084; kidney, P = 0.445). Interreader agreement was substantial with a kappa value of 0.78 (P < 0.001).

Conclusions
Diffusion-weighted imaging of the abdomen can be considerably accelerated and optimized integrating the SMS technique and a 3D diagonal diffusion mode. In a large patient cohort, this approach proved of superior image quality while maintaining similar ADC values compared with standard DWI. This technique seems applicable for daily clinical routine.
Estimating Autoantibody Signatures To Detect Autoimmune Disease Patient Subsets
Authors: Wu Zhenke , Casciola-Rosen Livia , Shah Ami A. , Rosen Antony , Zeger Scott L. 
Published: April 2017

SummaryAutoimmune diseases are characterized by highly specific immune responses against molecules in self-tissues. Different autoimmune diseases are characterized by distinct immune responses, making autoantibodies useful for diagnosis and prediction. In many diseases, the targets of autoantibodies are incompletely defined. Although the technologies for autoantibody discovery have advanced dramatically over the past decade, each of these techniques generates hundreds of possibilities, which are onerous and expensive to validate. We set out to establish a method to greatly simplify autoantibody discovery, using a pre-filtering step to define subgroups with similar specificities based on migration of radiolabeled, immunoprecipitated proteins on sodium dodecyl sulfate (SDS) gels and autoradiography [GelElectrophoresis and band detection onAutoradiograms (GEA)]. Human recognition of patterns is not optimal when the patterns are complex or scattered across many samples. Multiple sources of errors - including irrelevant intensity differences and warping of gels - have challenged automation of pattern discovery from autoradiograms.In this paper, we address these limitations using a Bayesian hierarchical model with shrinkage priors for pattern alignment and spatial dewarping. The Bayesian model combines information from multiple gel sets and corrects spatial warping for coherent estimation of autoantibody signatures defined by presence or absence of a grid of landmark proteins. We show the pre-processing creates more clearly separated clusters and improves the accuracy of autoantibody subset detection via hierarchical clustering. Finally, we demonstrate the utility of the proposed methods with GEA data from scleroderma patients.
A posteriori evaluation of molecular divergence dates using empirical estimates of time-heterogeneous fossilization rates
Authors: Gunkel Simon , Rust Jes , Wappler Torsten , Mayer Christoph , Niehuis Oliver , Misof Bernhard 
Published: April 2017

AbstractThe application of molecular clock concepts in phylogenetics permits estimating the divergence times of clades with an incomplete fossil record. However, the reliability of this approach is disputed, because the resulting estimates are often inconsistent with different sets of fossils and other parameters (clock models and prior settings) in the analyses. Here, we present the λ statistic, a likelihood approach fora posteriorievaluating the reliability of estimated divergence times. The λ statistic is based on empirically derived fossilization rates and evaluates the fit of estimated divergence times to the fossil record. We tested the performance of this measure with simulated data sets. Furthermore, we applied it to the estimated divergence times of (i) Clavigeritae beetles of the family Staphylinidae and (ii) all extant insect orders. The reanalyzed beetle data supports the originally published results, but shows that several fossil calibrations used do not increase the reliability of the divergence time estimates. Analyses of estimated inter-ordinal insect divergences indicate that uniform priors with soft bounds marginally outperform log-normal priors on node ages. Furthermore,a posteriorievaluation of the original published analysis indicates that several inter-ordinal divergence estimates might be too young. The λ statistic allows the comparative evaluation of any clade divergence estimate derived from different calibration approaches. Consequently, the application of different algorithms, software tools, and calibration schemes can be empirically assessed.
Estimated costs of implementing an open access policy at a private foundation
Authors: Strasser Carly , Khare Eesha 
Published: April 2017

AbstractBackgroundThe Gordon and Betty Moore Foundation (GBMF) was interested in understanding the potential effects of a policy requiring open access to peer-reviewed publications resulting from the research the foundation funds.MethodsWe collected data on more than 2000 publications in over 500 journals that were generated by GBMF grantees since 2001. We then examined the journal policies to establish how two possible open access policies might have affected grantee publishing habits.ResultsWe found that 99.3% of the articles published by grantees would have complied with a policy that requires open access within 12 months of publication. We also estimated the maximum annual costs to GBMF for covering fees associated with “gold open access” to be between $400,000 and $2,600,000 annually.DiscussionBased in part on this study, GBMF has implemented a new open access policy that requires grantees make peer-reviewed publications fully available within 12 months.
Not by systems alone: replicability assessment of disease expression signals
Authors: Ballouz Sara , Dörfel Max , Crow Megan , Crain Jonathan , Faivre Laurence , Keegan Catherine E. , Kitsiou-Tzeli Sophia , Tzetis Maria , Lyon Gholson J. , Gillis Jesse 
Published: April 2017

SummaryIn characterizing a disease, it is common to search for dysfunctional genes by assaying the transcriptome. The resulting differentially expressed genes are typically assessed for shared features, such as functional annotation or co-expression. While useful, the reliability of these systems methods is hard to evaluate. To better understand shared disease signals, we assess their replicability by first looking at gene-level recurrence and then pathway-level recurrence along with co-expression signals across six pedigrees of a rare homogeneous X-linked disorder,TAF1syndrome. We find most differentially expressed genes are not recurrent between pedigrees, making functional enrichment largely distinct in each pedigree. However, we find two highly recurrent “functional outliers” (CACNA1IandIGFBP3), genes acting atypically with respect to co-expression and therefore absent from a systems-level assessment. We show this occurs in re-analysis of Huntington’s disease, Parkinson’s disease and schizophrenia. Our results suggest a significant role for genes easily missed in systems approaches.