bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fido-SNP: the first webserver for scoring the impact of single nucleotide variants in the dog genome
Authors: Capriotti Emidio , Montanucci Ludovica , Profiti Giuseppe , Rossi Ivan , Giannuzzi Diana , Aresu Luca , Fariselli Piero 
Published: May 2019

Abstract
As the amount of genomic variation data increases, tools that are able to score the functional impact of single nucleotide variants become more and more necessary. While there are several prediction servers available for interpreting the effects of variants in the human genome, only few have been developed for other species, and none were specifically designed for species of veterinary interest such as the dog. Here, we present Fido-SNP the first predictor able to discriminate between Pathogenic and Benign single-nucleotide variants in the dog genome. Fido-SNP is a binary classifier based on the Gradient Boosting algorithm. It is able to classify and score the impact of variants in both coding and non-coding regions based on sequence features within seconds. When validated on a previously unseen set of annotated variants from the OMIA database, Fido-SNP reaches 88% overall accuracy, 0.77 Matthews correlation coefficient and 0.91 Area Under the ROC Curve.
RAD51 and mitotic function of mus81 are essential for recovery from low-dose of camptothecin in the absence of the WRN exonuclease
Authors: Aiello Francesca Antonella , Palma Anita , Malacaria Eva , Zheng Li , Campbell Judith L , Shen Binghui , Franchitto Annapaola , Pichierri Pietro 
Published: May 2019

Abstract
Stabilization of stalled replication forks prevents excessive fork reversal or degradation, which can undermine genome integrity. The WRN protein is unique among the other human RecQ family members to possess exonuclease activity. However, the biological role of the WRN exonuclease is poorly defined. Recently, the WRN exonuclease has been linked to protection of stalled forks from degradation. Alternative processing of perturbed forks has been associated to chemoresistance of BRCA-deficient cancer cells. Thus, we used WRN exonuclease-deficiency as a model to investigate the fate of perturbed forks undergoing degradation, but in a BRCA wild-type condition. We find that, upon treatment with clinically-relevant nanomolar doses of the Topoisomerase I inhibitor camptothecin, loss of WRN exonuclease stimulates fork inactivation and accumulation of parental gaps, which engages RAD51. Such mechanism affects reinforcement of CHK1 phosphorylation and causes persistence of RAD51 during recovery from treatment. Notably, in WRN exonuclease-deficient cells, persistence of RAD51 correlates with elevated mitotic phosphorylation of MUS81 at Ser87, which is essential to prevent excessive mitotic abnormalities. Altogether, these findings indicate that aberrant fork degradation, in the presence of a wild-type RAD51 axis, stimulates RAD51-mediated post-replicative repair and engagement of the MUS81 complex to limit genome instability and cell death.
A new normalization for Nanostring nCounter gene expression data
Authors: Molania Ramyar , Gagnon-Bartsch Johann A , Dobrovic Alexander , Speed Terence P 
Published: May 2019

AbstractThe Nanostring nCounter gene expression assay uses molecular barcodes and single molecule imaging to detect and count hundreds of unique transcripts in a single reaction. These counts need to be normalized to adjust for the amount of sample, variations in assay efficiency and other factors. Most users adopt the normalization approach described in the nSolver analysis software, which involves background correction based on the observed values of negative control probes, a within-sample normalization using the observed values of positive control probes and normalization across samples using reference (housekeeping) genes. Here we present a new normalization method, Removing Unwanted Variation-III (RUV-III), which makes vital use of technical replicates and suitable control genes. We also propose an approach using pseudo-replicates when technical replicates are not available. The effectiveness of RUV-III is illustrated on four different datasets. We also offer suggestions on the design and analysis of studies involving this technology.
HIV Coinfection Predicts Failure of Ledipasvir/Sofosbuvir in Treatment-Naïve Noncirrhotic Patients With HCV Genotype 1
Authors: Berenguer Juan , Calleja José Luis , Montes María Luisa , Gil Ángela , Moreno Ana , Bañares Rafael , Aldámiz-Echevarría Teresa , Albillos Agustín , Téllez María Jesús , Olveira Antonio , Domínguez Lourdes , Fernández Inmaculada , García-Samaniego Javier , Polo Benjamín A , Álvarez Beatriz , Ryan Pablo , Barrio José , Devesa María J , Benítez Laura , Santos Ignacio , Buey Luisa García , Sanz José , Poves Elvira , Losa Juan E , Fernández-Rodríguez Conrado , Jarrín Inmaculada , Calvo María J , González-García Juan 
Published: May 2019

Abstract

Background
The efficacy of licensed direct-acting antiviral (DAA) regimens is assumed to be the same for hepatitis C virus (HCV)–monoinfected patients (HCV-Mono) and HIV/HCV-coinfected patients (HCV-Co). However, the high sustained viral response (SVR) rates of DAA regimens and the small number of HIV-infected patients included in registration trials have made it difficult to identify predictors of treatment failure, including the presence of HIV.

Methods
We compared treatment outcomes for ledipasvir/sofosbuvir (LDV/SOF) against HCV G1 in treatment-naïve HCV-Mono and HCV-Co without cirrhosis in a prospective registry of individuals receiving DAAs for HCV.

Results
Up to September 2017, a total of 17 269 patients were registered, and 1358 patients (1055 HCV-Mono/303 HCV-Co) met the inclusion criteria. Significant differences between HCV-Mono and HCV-Co were observed for age, gender, and G1 subtype distribution. Among HCV-Co, 99.0% were receiving antiretroviral therapy. SVR rates for LDV/SOF at 8 weeks did not differ significantly between HCV-Mono and HCV-Co (96.9% vs 94.0%; P = .199). However, the SVR rate for LDV/SOF at 12 weeks was significantly higher for HCV-Mono than HCV-Co (97.2% vs 91.8%; P = .001). A multivariable logistic regression model including age, sex, liver stiffness, G1 subtype, HCV-RNA, HIV, and treatment duration showed the factors associated with treatment failure to be male sex (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.27–4.91; P = .008) and HIV infection (aOR, 2.23; 95% CI, 1.13–4.38; P = .020).

Conclusions
The results of this large prospective study analyzing outcomes for LDV/SOF against HCV G1 in treatment-naïve noncirrhotic patients suggest that HIV infection is a predictor of treatment failure in patients with chronic hepatitis C.
Treatment Duration and Associated Outcomes for Skin and Soft Tissue Infections in Patients With Obesity or Heart Failure
Authors: Ihm Claudia , Sutton Jesse D , Timbrook Tristan T , Spivak Emily S 
Published: May 2019

AbstractBackgroundAlthough existing literature supports durations of 5–7 days for skin and soft tissue infections (SSTIs), longer durations are commonly used. Obesity and heart failure (HF) have been associated with increased risk for treatment failure of SSTIs; however, whether prolonged antibiotic durations reduce the risk of treatment failure is unknown. We evaluated practice patterns for SSTIs in patients with obesity and/or HF and whether short antibiotic durations (≤8 days) were associated with treatment failure.MethodsWe performed a single-center, retrospective cohort study of inpatients between January 1, 2006, and December 30, 2016, with SSTIs based on International Classification of Diseases (ICD) coding, and obesity and/or HF. Charts were manually reviewed to collect demographic, clinical, treatment, and outcome data. Propensity score matching was used to estimate the risk of treatment failure between the 2 groups. Secondary outcomes included length of stay, 30-day readmission, and Clostridium difficile infection rates.ResultsA total of 207 patients were included. Forty-nine (23.7%) received a short antibiotic duration and 158 (76.3%) a long duration. The median duration of therapy (interquartile range [IQR]) was 7 (7–8) days in the short group and 14 (10–15) days in the long group. In the propensity score–matched cohort, 28 (28.6%) treatment failures occurred in the long group, as compared with 5 (10.2%) in the short group (P = .02), as well as a shorter length of stay (IQR) in the short- vs long-duration group (2 [2–3] vs 3 [2–5] days, respectively; P = .002). There was no difference in other secondary outcomes.ConclusionsThe majority of patients with obesity or HF received a longer antibiotic course for SSTIs; however, a longer antibiotic course was not associated with lower treatment failure rates. Higher failure rates in the long-duration group may be reflective of clinical decisions made in the face of diagnostic uncertainty and warrant further evaluation.
Religious Origins and Modern Legal Norms: A Dialectical Account
Authors: Mauldin Joshua T 
Published: May 2019

Abstract
A significant amount of scholarship in the field of law and religion involves tracing the sources of contemporary legal and political norms to historical religious traditions. But the relationship between historical religious traditions and modern legal norms is often implicit and undertheorized. This article examines three examples of leading scholars who trace the influence of religious ideas to legal norms in strikingly different ways. Highlighting the work of Martha Nussbaum, Jeremy Waldron, and Samuel Moyn helps bring to rational articulation the normative decisions that are made in attempts to trace historical religious traditions to the contemporary norms that shape modern legal systems.
Endoscopic Fluorescence-Guided Resection Increases Radicality in Glioblastoma Surgery
Authors: Bettag Christoph , Hussein Abdelhalim , Behme Daniel , Maragkou Theoni , Rohde Veit , Mielke Dorothee 
Published: May 2019

Abstract

BACKGROUND
Several studies have proven the benefit of a greater extent of resection on progression-free survival and overall survival in glioblastoma (GBM). Possible reasons for incomplete tumor resection might be wrong interpretation of fading fluorescence or overseen fluorescent tumor tissue by a lacking line of sight between tumor tissue and the microscope.

OBJECTIVE
To evaluate if an endoscope being capable of inducing fluorescence might overcome some limitations of microscopic fluorescence-guided (FG) resection.

METHODS
5-Aminolevulinic acid (20 mg/kg) was given 4 h before surgery. Microsurgical resection of all fluorescent tissue was performed. Then, the resection cavity was scanned with the endoscope. Fluorescent tissue, not being visualized by the microscope, was additionally removed and histopathologically examined separately. Neuronavigation was used for defining the sites of additional tumor resection. All patients underwent magnetic resonance imaging within 48 h after surgery.

RESULTS
Twenty patients with GBM were operated using microscopic and endoscopic FG resection. In all patients, additional fluorescent tissue was detected with the endoscope. This tissue was completely resected in 19 patients (95%). Eloquent localization precluded complete resection in the remaining patient. In 19 patients (95%), histopathological examination confirmed tumor in the additionally resected tissue. In 19 patients (95%), complete resection was confirmed. In all patients, endoscopic FG resection reached beyond the borders of contrast-enhancing tumor.

CONCLUSION
Endoscopic FG resection of GBM allows increasing the complete resection rate substantially and therefore is a useful adjunct to microscopic FG resection.
Understanding further education as a context for public health intervention: qualitative findings from a study process evaluation
Authors: Langford R , Willmott M , Fletcher A 
Published: May 2019

Abstract

Background
Over 1.2 million 16–18 year-olds are enrolled in further education (FE—advanced secondary education) in England. Life course transitions provide opportunities to change, establish or reinforce health behaviours. FE presents an opportunity for public health improvement, yet few interventions target this setting. Using a smoking prevention intervention, we explore how young people were viewed in FE and how this affected intervention acceptability.

Methods
Eleven student and five staff focus groups were conducted in three intervention institutions (two colleges, one school sixth-form), as part of the process evaluation of a smoking prevention feasibility study. FE managers in intervention and control institutions were also interviewed (n = 5). Data were analysed using thematic analysis.

Results
In both colleges and the sixth-form, students were viewed as emergent adults and treated differently from ‘school-children’, in practice if not in policy. Colleges permitted smoking in designated areas; in the school sixth-form smoking was unofficially tolerated but concealed from younger students. Using staff to deliver anti-smoking messages reintroduced an unwanted power dynamic which disrupted perceptions of students as young adults.

Conclusions
FE is an important setting for young people’s health. Understanding the culture and context of FE is critical in designing acceptable and effective public health interventions.
Effectiveness of public procurement of innovation versus supply-side innovation measures in manufacturing and service sectors
Authors: Radicic Dragana 
Published: May 2019

AbstractMost quantitative evaluations report positive but small effects of supply-side innovation measures. Although the literature suggests that demand-side measures, in particular, public procurement of innovation, might be more effective in stimulating innovation than supply-side measures, empirical evidence on this proposition is scarce. To empirically test this proposition, we utilize the Eurobarometer 2014 survey to estimate the effects from public procurement of innovation as well as from the supply-side innovation measures on product and process innovations in manufacturing and service firms in the USA and Europe. Our findings suggest that the treatment effects of public procurement of innovation are indeed larger than the effects of supply-side public support on product innovation in both manufacturing and service sectors. This finding also holds for process innovation, but only in the service sector. In contrast, in manufacturing firms, the estimated effects on process innovation are only positive and significant in firms receiving public support.
The transcriptional activity of a temperature-sensitive transcription factor module is associated with pollen shedding time in pine
Authors: Niu Shi-Hui , Liu Shuang-Wei , Ma Jing-Jing , Han Fang-Xu , Li Yue , Li Wei 
Published: May 2019

AbstractIt has long been known that the pollen shedding time in pine trees is correlated with temperature, but the molecular basis for this has remained largely unknown. To better understand the mechanisms driving temperature response and to identify the hub regulators of pollen shedding time regulation in Pinus tabuliformis Carr., we identified a set of temperature-sensitive genes by carrying out a comparative transcriptome analysis using six early pollen shedding trees (EPs) and six late pollen shedding trees (LPs) during mid-winter and at three consecutive time points in early spring. We carried out a weighted gene co-expression network analysis and constructed a transcription factor (TF) collaborative network, merging the common but differentially expressed TFs of the EPs and LPs into a joint network. We found five hub genes in the core TF module whose expression was rapidly induced by low temperatures. The transcriptional activity of this TF module was strongly associated with pollen shedding time, and likely to produce the fine balance between cold hardiness and growth activity in early spring. We confirmed the key role of temperature in regulating flowering time and identified a transcription factor module associated with pollen shedding time in P. tabuliformis. This suggests that repression of growth activity by repressors is the main mechanism balancing growth and cold hardiness in pine trees in early spring. Our results provide new insights into the molecular mechanisms regulating seasonal flowering time in pines.
Epidemiology and distribution of Plasmodium vivax malaria in Sudan
Authors: Elgoraish Amanda G , Elzaki Salah Eldin G , Ahmed Rania TagElsir , Ahmed Arwa Ibrahim , Fadlalmula Huda A , Abdalgader Mohamed Shymaa , Abdallah Nusiba I , Abdelgadir Osman , Ageep Tellal B , El-Sayed Badria B 
Published: May 2019

Abstract

Background
Plasmodium vivax malaria has been recognised as an important cause of morbidity in several African countries. The prevalence was previously estimated as 2–5% in eastern Sudan. These estimates are observed to be rising and spreading continuously. The present study was undertaken to investigate the situation of distribution and epidemiology of P. vivax malaria in Sudan.

Methods
Cross-sectional malaria surveys carried out in hospitals and health centres covered 21 sites in 10 states. Data and blood samples were collected from 1226 clinically investigated suspected malaria cases of both genders and all ages. Microscopically detected malaria parasites were confirmed by PCR.

Results
The overall prevalence of P. vivax among the malaria cases was 26.6%. The prevalence showed significant variations between the states (p<0.001), which could be explained by differences in population movement, the presence of refugees and proximity to endemic neighbouring countries. It also varied significantly with residence status (p<0.001), reflecting the stability of transmission.

Conclusion
Although malaria in Sudan is still largely attributed to Plasmodium falciparum, P. vivax has been rising with worrying proportions and spreading to new areas. The emergence and marked increase of P. vivax poses new challenges to malaria treatment and control in Sudan.
The influence of visual experience and cognitive goals on spatial representations of nociceptive stimuli
Authors: Vanderclausen Camille , Manfron Louise , De Volder Anne , Legrain Valéry 
Published: May 2019

AbstractLocalizing pain is an important process as it allows detecting which part of the body is being hurt and identifying in its surrounding which stimulus is producing the damage. Nociceptive inputs should therefore be mapped according to both somatotopic (“which limb is stimulated?”) and spatiotopic representations (“where is the stimulated limb?”). Since the limbs constantly move in space, the brain has to realign the different spatial representations, for instance when the hands are crossed and the left/right hand is in the right/left part of space, in order to adequately guide actions towards the threatening object. Such ability is thought to be dependent on past sensory experience and contextual factors. This was tested by comparing performances of early blind and normally sighted participants during nociceptive temporal order judgment tasks. The instructions prioritized either anatomy (left/right hands) or the external space (left/right hemispaces). As compared to an uncrossed hands posture, sighted participants’ performances were decreased when the hands were crossed, whatever the instructions. Early blind participants’ performances were affected by crossing the hands only during spatial instruction, but not during anatomical instruction. These results indicate that nociceptive stimuli are automatically coded according to both somatotopic and spatiotopic representations, but the integration of the different spatial reference frames would depend on early visual experience and ongoing cognitive goals, illustrating the plasticity and the flexibility of the nociceptive system.
Photoreceptor inputs to pupil control
Authors: Spitschan Manuel 
Published: May 2019

AbstractThe size of the pupil depends on light level. Watson & Yellott (2012) developed a unified formula to predict pupil size from luminance, field diameter, age, and number of eyes. Luminance reflects input from the L and M cones in the retina but ignores the contribution of intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin, which are known to control the size of the pupil. We discuss the role of melanopsin in controlling pupil size by reanalysing an extant data set. We confirm that melanopsin-weighted quantities, in conjunction with Watson & Yellott’s formula, adequately model intensity-dependent pupil size. We discuss the contributions of other photoreceptors into pupil control.
Auditory cortical alpha desynchronization prioritizes the representation of memory items during a retention period
Authors: Kraft Nadine , Demarchi Gianpaolo , Weisz Nathan 
Published: May 2019

AbstractMaintaining information in working memory normally happens in dynamic environments, with a multitude of distracting events. This is particularly evident in the auditory system, for example, when trying to memorize a telephone number during ongoing background noise. How relevant to-be-memorized information is protected against the adverse influence of a temporally predictable distractor was the main goal of the present study. For this purpose we adapted a Sternberg task variant established in the visual modality, with either a strong or a weak distracting sound presented at a fixed time during the retention period. Our behavioral analysis confirmed a small, albeit significant deterioration of memory performance in the strong distractor condition. We used a time-generalized decoding approach applied to magnetoencephalography (MEG) data to investigate the extent of memory probe-related information prior to the anticipated distractor onset and found a relative decrease for the strong distractor condition. This effect was paralleled by a pre-distractor alpha power decrease in the left superior temporal gyrus (STG), a cortical region putatively holding memory content relevant information. Based on gating frameworks of alpha oscillations, these results could be interpreted as a failed inhibition of an anticipated strong (more salient) distractor. However, in a critical analysis we found that reduced alpha power in the left STG was associated with relatively increased memory probe-related information. Our results therefore support the view of alpha power reductions in relevant sensory (here auditory) cortical areas to be a mechanism by which to-be-remembered information is prioritized during working memory retention periods.
Recapitulation and Retrospective Prediction of Biomedical Associations Using Temporally-enabled Word Embeddings
Authors: Park Jiho , Marquez Agustin Lopez , Puranik Arjun , Rajasekharan Ajit , Aravamudan Murali , Garcia-Rivera Enrique 
Published: May 2019

AbstractThe recent explosion of biomedical knowledge presents both a major opportunity and challenge for scientists tackling complex problems in healthcare. Here we present an approach for synthesizing biomedical knowledge based on a combination of word-embeddings and select cooccurrences. We evaluated our ability to recapitulate and retrospectively predict disease-gene associations from the Online Mendelian Inheritance in Man (OMIM) resource. Our metrics achieved an area under the curve (AUC) value of 0.981 at the recapitulation task for 2,400 disease-gene associations. At the most stringent cutoff, our metrics predicted 13.89% of these associations before their first cooccurrence in the literature, with a median time of 4 years between prediction and first cooccurrence. Finally, our literature metrics can be combined with human genetics data to retrospectively predict disease-gene associations, IL-6 and Giant Cell Arteritis provided as an example. We believe this framework can provide robust biomedical hypotheses at a much faster pace than current standard practices.