bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restoring effects of oxytocin on the attentional preference for faces in autism
Authors: Kanat M , Spenthof I , Riedel A , van Elst L T , Heinrichs M , Domes G 
Published: April 2017

AbstractReduced attentional preference for faces and symptoms of social anxiety are common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers anxiolytic functions and enhances eye gaze, facial emotion recognition and neural correlates of face processing in ASD. Here we investigated whether a single dose of oxytocin increases attention to faces in ASD. As a secondary question, we explored the influence of social anxiety on these effects. We tested for oxytocin’s effects on attention to neutral faces as compared to houses in a sample of 29 autistic individuals and 30 control participants using a dot-probe paradigm with two different presentation times (100 or 500 ms). A single dose of 24 IU oxytocin was administered in a randomized, double-blind placebo-controlled, cross-over design. Under placebo, ASD individuals paid less attention to faces presented for 500 ms than did controls. Oxytocin administration increased the allocation of attention toward faces in ASD to a level observed in controls. Secondary analyses revealed that these oxytocin effects primarily occurred in ASD individuals with high levels of social anxiety who were characterized by attentional avoidance of faces under placebo. Our results confirm a positive influence of intranasal oxytocin on social attention processes in ASD. Further, they suggest that oxytocin may in particular restore the attentional preference for facial information in ASD individuals with high social anxiety. We conclude that oxytocin’s anxiolytic properties may partially account for its positive effects on socio-cognitive functioning in ASD, such as enhanced eye gaze and facial emotion recognition.
Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
Authors: Hägg S , Zhan Y , Karlsson R , Gerritsen L , Ploner A , van der Lee S J , Broer L , Deelen J , Marioni R E , Wong A , Lundquist A , Zhu G , Hansell N K , Sillanpää E , Fedko I O , Amin N A , Beekman M , de Craen A J M , Degerman S , Harris S E , Kan K-J , Martin-Ruiz C M , Montgomery G W ,   NeuroCHARGE Cognitive Working Group, Adolfsson A N , Reynolds C A , Samani N J , Suchiman H E D , Viljanen A , von Zglinicki T , Wright M J , Hottenga J-J , Boomsma D I , Rantanen T , Kaprio J A , Nyholt D R , Martin N G , Nyberg L , Adolfsson R , Kuh D , Starr J M , Deary I J , Slagboom P E , van Duijn C M , Codd V , Pedersen N L ,   for the ENGAGE Consortium
Published: April 2017

AbstractThe association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=−0.053; 95% CI: −0.087, −0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10−5), whereas carriers performed better in STROOP (β=−0.074; 95% CI: −0.140, −0.009; P=0.03). Causal associations were found for STROOP only (β=−0.598 per s.d.-increase of TL; 95% CI: −1.125, −0.072; P=0.026), with a larger effect in ɛ4-carriers (β=−0.699; 95% CI: −1.330, −0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.
Experimental dispersal reveals characteristic scales of biodiversity in a natural landscape
Authors: Germain Rachel M. , Strauss Sharon Y. , Gilbert Benjamin 
Published: April 2017

Significance
Biological communities differ dramatically in numbers and identities of species, a pattern that could be explained by many mechanisms that each vary with spatial scale. Testing how ecological mechanisms transition among scales is key to understanding the maintenance of diversity but is infeasible in most systems. In a natural plant community, we experimentally enhanced seed dispersal over scales ranging from 1 m to 10 km using a seed vacuum. Our results indicate that pervasive dispersal limitation constrains local communities at and above 100 m, causing communities to contain half as many species as the environment is capable of supporting. Our results suggest that many species at risk for extirpation in this global biodiversity hotspot could be restored through managed dispersal.
Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson’s disease
Authors: Kouroupi Georgia , Taoufik Era , Vlachos Ioannis S. , Tsioras Konstantinos , Antoniou Nasia , Papastefanaki Florentia , Chroni-Tzartou Dafni , Wrasidlo Wolfgang , Bohl Delphine , Stellas Dimitris , Politis Panagiotis K. , Vekrellis Kostas , Papadimitriou Dimitra , Stefanis Leonidas , Bregestovski Piotr , Hatzigeorgiou Artemis G. , Masliah Eliezer , Matsas Rebecca 
Published: April 2017

Significance
Parkinson’s disease (PD) is an incurable neurodegenerative disorder characterized by motor and nonmotor deficits, including cognitive decline and dementia. The protein αSyn is strongly associated with PD pathogenesis, whereas αSyn mutations, such as p.A53T, cause familial forms of PD. Animal models are crucial for understanding PD pathogenesis, but there are limitations in the extent to which these models reproduce faithfully the human disease. Cell-reprogramming technologies allow the generation of human neurons from patients with PD, but it has proven difficult to identify cellular pathologies in induced pluripotent stem cell–derived neurons. In this study, we created a robust p.A53T patient–derived model of PD that captures disease-related phenotypes under basal conditions, thus providing a unique system for studies of disease mechanisms and development of therapeutics.
NGF-TrkA signaling in sensory nerves is required for skeletal adaptation to mechanical loads in mice
Authors: Tomlinson Ryan E. , Li Zhi , Li Zhu , Minichiello Liliana , Riddle Ryan C. , Venkatesan Arun , Clemens Thomas L. 
Published: April 2017

Significance
Peripheral sensory nerves expressing TrkA, the high-affinity receptor for NGF, densely innervate the surfaces of long bones, a privileged location for the regulation of biomechanical signaling. In this study, we used several genetically engineered mouse models to examine the role of NGF-TrkA signaling in skeletal adaptation to mechanical loads. Our results support a model in which mechanical signals up-regulate the expression of NGF in osteoblasts on the bone surface that, in turn, activates TrkA sensory nerves, leading to the release of osteogenic cues that modulate osteocytic Wnt/β-catenin signaling and support bone formation.
Insect haptoelectrical stimulation of Venus flytrap triggers exocytosis in gland cells
Authors: Scherzer Sönke , Shabala Lana , Hedrich Benjamin , Fromm Jörg , Bauer Hubert , Munz Eberhard , Jakob Peter , Al-Rascheid Khaled A. S. , Kreuzer Ines , Becker Dirk , Eiblmeier Monika , Rennenberg Heinz , Shabala Sergey , Bennett Malcolm , Neher Erwin , Hedrich Rainer 
Published: April 2017

SignificanceThe Venus flytrap has been in the focus of scientists since Darwin’s time. Carnivorous plants, with their specialized lifestyle, including insect capture, as well as digestion and absorption of prey, developed unique tools to gain scarce nutrients. In this study, we describe mechanistic insights into the cascade of events following the capture of insect prey. Action potentials evoked by the struggling prey are translated into touch-inducible hormone signals that promote the formation of secretory vesicles. Different varieties of digestive compounds are released sequentially into the flytrap’s “green stomach” and break down the captured animal. Amperometry provides insight into the kinetics and chemistry of the stimulus-coupled glandular secretion process.
Reconstructed ancestral enzymes suggest long-term cooling of Earth’s photic zone since the Archean
Authors: Garcia Amanda K. , Schopf J. William , Yokobori Shin-ichi , Akanuma Satoshi , Yamagishi Akihiko 
Published: April 2017

Significance
Geological evidence suggesting that Earth's oceans cooled from ∼55–85 °C in the Archean (∼3,500 Ma) to the present has met with skepticism due to possible geochemical alteration of the rocks analyzed and uncertainties about their depositional environment. Determination of the thermostability of experimentally reconstructed ancestral enzymes provides independent means to assess paleotemperature. Because some previously analyzed taxa may have inhabited atypically high-temperature environments (e.g., deep-sea hydrothermal vents), we have restricted our analyses to ancestral enzymes reconstructed from photic-zone cyanobacteria and land plants. Our findings indicate a cooling of Earth's surface temperature from ∼75 °C in the Archean (∼3,000 Ma) to ∼35 °C in the Devonian (∼420 Ma), consistent with previous geological and enzyme-based results.
Denoising genome-wide histone ChIP-seq with convolutional neural networks
Authors: Koh Pang Wei , Pierson Emma , Kundaje Anshul 
Published: April 2017

Abstract

Motivation
Chromatin immune-precipitation sequencing (ChIP-seq) experiments are commonly used to obtain genome-wide profiles of histone modifications associated with different types of functional genomic elements. However, the quality of histone ChIP-seq data is affected by many experimental parameters such as the amount of input DNA, antibody specificity, ChIP enrichment and sequencing depth. Making accurate inferences from chromatin profiling experiments that involve diverse experimental parameters is challenging.

Results
We introduce a convolutional denoising algorithm, Coda, that uses convolutional neural networks to learn a mapping from suboptimal to high-quality histone ChIP-seq data. This overcomes various sources of noise and variability, substantially enhancing and recovering signal when applied to low-quality chromatin profiling datasets across individuals, cell types and species. Our method has the potential to improve data quality at reduced costs. More broadly, this approach—using a high-dimensional discriminative model to encode a generative noise process—is generally applicable to other biological domains where it is easy to generate noisy data but difficult to analytically characterize the noise or underlying data distribution.

Availability and implementation
https://github.com/kundajelab/coda.
Assessment of the Albumin-Bilirubin (ALBI) Grade as a Prognostic Indicator for Hepatocellular Carcinoma Patients Treated With Radioembolization
Authors: Gui Bin , Weiner Ashley A. , Nosher John , Lu Shou-En , Foltz Gretchen M. , Hasan Omar , Kim Seung K. , Gendel Vyacheslav , Mani Naganathan B. , Carpizo Darren R. , Saad Nael E. , Kennedy Timothy J. , Zuckerman Darryl A. , Olsen Jeffrey R. , Parikh Parag J. , Jabbour Salma K. 
Published: April 2017

Objective:
As the utility of Child-Pugh (C-P) class is limited by the subjectivity of ascites and encephalopathy, we evaluated a previously established objective method, the albumin-bilirubin (ALBI) grade, as a prognosticator for yttrium-90 radioembolization (RE) treatment for patients with hepatocellular carcinoma (HCC).

Materials and Methods:
A total of 117 patients who received RE for HCC from 2 academic centers were reviewed and stratified by ALBI grade, C-P class, and Barcelona Clinic Liver Cancer stage. The overall survival (OS) according to these 3 criteria was evaluated by Kaplan-Meier survival analysis. The utilities of C-P class and ALBI grade as prognostic indicators were compared using the log-rank test. Multivariate Cox regression analysis was performed to identify additional predictive factors.

Results:
Patients with ALBI grade 1 (n=49) had superior OS than those with ALBI grade 2 (n=65) (P=0.01). Meanwhile, no significant difference was observed in OS between C-P class A (n=100) and C-P class B (n=14) (P=0.11). For C-P class A patients, the ALBI grade (1 vs. 2) was able to stratify 2 clear and nonoverlapping subgroups with differing OS curves (P=0.03). Multivariate Cox regression test identified alanine transaminase, Barcelona Clinic Liver Cancer stage, and ALBI grade as the strongest prognostic factors for OS (P<0.10).

Conclusions:
ALBI grade as a prognosticator has demonstrated clear survival discrimination that is superior to C-P class among HCC patients treated with RE, particularly within the subgroup of C-P class A patients. ALBI grade is useful for clinicians to make decisions as to whether RE should be recommended to patients with HCC.
Persistence of Hepatitis B Immunity Following 3-dose Infant Primary Series in HIV-infected Thai Adolescents and Immunologic Response to Revaccination
Authors: Lapphra Keswadee , Angkhananukit Paveena , Saihongthong Supawan , Phongsamart Wanatpreeya , Wittawatmongkol Orasri , Rungmaitree Supattra , Chokephaibulkit Kulkanya 
Published: April 2017

Background:
HIV infection may alter immunologic response and the establishment of immune memory to infant hepatitis B virus (HBV) vaccination. This study aimed to determine the need to revaccinate perinatally HIV-infected Thai adolescents.

Methods:
Cross-sectional serologic tests for HBV, including hepatitis B surface antigen, anti-hepatitis B surface antibody (anti-HBs) and anti-hepatitis B core antibody (anti-HBc), were performed in perinatally HIV-infected adolescents. Adolescents having anti-HBs <100 mIU/mL with negative anti-HBc and immune reconstitution from highly active antiretroviral therapy (HAART) were revaccinated using regular (10 μg) 3-dose schedule given intramuscularly at 0-, 2- and 6-month intervals.

Results:
Of 193 adolescents who received 3-dose infant HBV vaccination, 6 were receiving HAART during vaccination, median (interquartile range) current age 14.5 (11.7–16.2) years, 7 (3.6%) had positive anti-HBc (indicating breakthrough infection), of which 4 (2%) had positive hepatitis B surface antigen (indicating chronic infection). Twenty-two (11.4%) adolescents had protective anti-HBs concentration >10 mIU/mL. Of 164 revaccinated adolescents, 142 (86.6%) had HIV viral load <40 copies/mL. Anti-HBs seroconversion rates >10 mIU/mL were 58.0% (94/162) after the first dose and 97.5% (158/162) after the third dose of revaccination. Forty-five (28%) subjects responded to the first dose with anti-HBs antibody ≥100 mIU/mL had a shorter median duration with CD4 count <15% than their counterparts (6.2 vs. 11.1 months; P = 0.049).

Conclusions:
Only half of perinatally HIV-infected adolescents were able to elicit anti-HBs response with a single-dose HBV vaccine. Revaccination with 3-dose schedule is required in perinatally HIV-infected adolescents who did not initiate HAART at the time of infant vaccination.
Single-Center Study Investigating Foreign Language Acquisition at School in Children, Adolescents, and Young Adults With Uni- or Bilateral Cochlear Implants in the Swiss German Population
Authors: Beeres-Scheenstra Renske , Ohnsorg Claudia , Candreia Claudia , Heinzmann Sybille , Castellanos Susana , De Min Nicola , Linder Thomas E. 
Published: April 2017

Objective:
To evaluate foreign language acquisition at school in cochlear implant patients.

Study Design:
Cohort study.

Setting:
CI center.

Patients:
Forty three cochlear implants (CI) patients (10–18 yr) were evaluated. CI nonusers and patients with CI-explantation, incomplete datasets, mental retardation, or concomitant medical disorders were excluded.

Intervention(s):
Additional data (type of schooling, foreign language learning, and bilingualism) were obtained with questionnaires. German-speaking children with foreign tuition language (English and/or French) at school were enrolled for further testing.

Main Outcome Measure(s):
General patient data, auditory data, and foreign language data from both questionnaires and tests were collected and analyzed.

Results:
Thirty seven out of 43 questionnaires (86%) were completed. Sixteen (43%) were in mainstream education. Twenty-seven CI users (73%) have foreign language learning at school. Fifteen of these were in mainstream education (55%), others in special schooling. From 10 CI users without foreign language learning, one CI user was in mainstream education (10%) and nine patients (90%) were in special schooling. Eleven German-speaking CI users were further tested in English and six additionally in French. For reading skills, the school objectives for English were reached in 7 of 11 pupils (64%) and for French in 3 of 6 pupils (50%). For listening skills, 3 of 11 pupils (27%) reached the school norm in English and none in French.

Conclusions:
Almost 75% of our CI users learn foreign language(s) at school. A small majority of the tested CI users reached the current school norm for in English and French in reading skills, whereas for hearing skills most of them were not able to reach the norm.
The Application of Next-Generation Sequencing for Mutation Detection in Autosomal-Dominant Hereditary Hearing Impairment
Authors: Gürtler Nicolas , Röthlisberger Benno , Ludin Katja , Schlegel Christoph , Lalwani Anil K. 
Published: April 2017

Objective:
Identification of the causative mutation using next-generation sequencing in autosomal-dominant hereditary hearing impairment, as mutation analysis in hereditary hearing impairment by classic genetic methods, is hindered by the high heterogeneity of the disease.

Patients:
Two Swiss families with autosomal-dominant hereditary hearing impairment.

Intervention:
Amplified DNA libraries for next-generation sequencing were constructed from extracted genomic DNA, derived from peripheral blood, and enriched by a custom-made sequence capture library. Validated, pooled libraries were sequenced on an Illumina MiSeq instrument, 300 cycles and paired-end sequencing. Technical data analysis was performed with SeqMonk, variant analysis with GeneTalk or VariantStudio. The detection of mutations in genes related to hearing loss by next-generation sequencing was subsequently confirmed using specific polymerase-chain-reaction and Sanger sequencing.

Main Outcome Measure:
Mutation detection in hearing-loss-related genes.

Results:
The first family harbored the mutation c.5383+5delGTGA in the TECTA-gene. In the second family, a novel mutation c.2614-2625delCATGGCGCCGTG in the WFS1-gene and a second mutation TCOF1-c.1028G>A were identified.

Conclusion:
Next-generation sequencing successfully identified the causative mutation in families with autosomal-dominant hereditary hearing impairment. The results helped to clarify the pathogenic role of a known mutation and led to the detection of a novel one. NGS represents a feasible approach with great potential future in the diagnostics of hereditary hearing impairment, even in smaller labs.
The Effect of Elevated Intracranial Pressure on Frequency Tuning of Air-Conducted Ocular Vestibular Myogenic Potentials in Ménière's Disease Patients
Authors: Maxwell Rebecca , Jerin Claudia , Gürkov Robert 
Published: April 2017

Objective:
To investigate the effect of increased intracranial pressure on ocular vestibular-evoked myogenic potential (oVEMP) amplitudes and frequency tuning in patients with Ménière's disease (MD) to elucidate whether oVEMPS recorded under such conditions could provide a simple and accurate diagnostic test for MD.

Setting:
Tertiary referral center for otology and neurotology.

Patients:
Ten patients with certain unilateral MD (mean age = 48.2 yr, range 25–75 yr, 6 males and 4 females) as confirmed by a locally enhanced inner ear MRI (LEIM) were enrolled in this study.

Design:
Air-conducted tone-burst oVEMP amplitudes were measured in response to 500 Hz and 1000 Hz in the horizontal plane (0 degree), a 20-degree head-down position.

Results:
Tilting the patients from the horizontal position to the 20-degree head-down position led to a large reduction in oVEMP amplitudes to the 500 Hz tone burst (3.02 μV vs 1.17 μV, p = 0.005) and to a smaller one in the 1000 Hz tone burst (2.28 μV vs 1.78 μV, p = 0.013) in the Ménière's ear. Accordingly, the 500/1000 Hz frequency–tuning ratio was significantly decreased in the Ménière's ear as a result of this manoeuver (1.36 vs 0.75, p = 0.005).

Conclusion:
oVEMP amplitudes and frequency tuning in MD patients show a similar behavior to that found in healthy control subjects. oVEMP testing of putative MD patients in the tilted position is therefore unlikely to be diagnostically useful.
HIV-Specific CD8 T Cells Producing CCL-4 Are Associated With Worse Immune Reconstitution During Chronic Infection
Authors: Casetti Rita , Pinnetti Carmela , Sacchi Alessandra , De Simone Gabriele , Bordoni Veronica , Cimini Eleonora , Tumino Nicola , Besi Francesca , Viola Domenico , Turchi Federica , Mazzotta Valentina , Antinori Andrea , Martini Federico , Ammassari Adriana , Agrati Chiara 
Published: April 2017

Background:
Immunological nonresponse represents the Achilles heel in the combination antiretroviral therapy (cART) effectiveness, and increases risk of clinical events and death. CD8 T cells play a crucial role in controlling HIV replication, and polyfunctional HIV-specific CD8 T cells have been associated with nonprogressive HIV infection. However, the possible role of polyfunctional CD8 T cells in predicting posttreatment immune reconstitution has not yet been explored. The aim of this study was to identify functional markers predictive of immunological response to cART in chronic HIV-infected patients.

Methods:
A cohort of chronic HIV-infected individuals naive to cART were enrolled in the ALPHA study. CD4/CD8 T-cell subsets, their differentiation/activation, as well as susceptibility to apoptosis were analyzed before and after 12 months of cART. Moreover, CD8 T cells polyfunctional response after HIV antigenic stimulation was also assessed.

Results:
Results showed a significant correlation between worse CD4 T-cell restoration and low frequency of naive CD4 T cells, high frequency of effector memory CD4 T cells, and high susceptibility to apoptosis of CD4 T cells all before cART. Moreover, CD8 functional subsets expressing total C-C motif chemokine ligand 4 (CCL-4) or in combination with CD107a and interferon gamma (IFNγ) were negatively associated with immune reconstitution.

Conclusions:
In conclusion, our study shows that a more differentiated phenotype of CD4 T cells and CCL-4–producing CD8 T cells could represent valuable predictors of worse immune reconstitution. These parameters may be used as tools for identifying patients at risk of immunological failure during cART and eventually represent the basis for innovative therapeutic strategies.