bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intellectual Disability in the European Middle Ages
Authors: Metzler Irina 
Published: July 2018

Abstract
This investigation of intellectual disability in the Middle Ages uncovers narratives of this perceived condition in the historical sources. Authors of normative texts, for instance, medical, legal, and natural-philosophical authorities, were the medieval equivalent of modern scientific experts with regard to defining, assessing, and controlling notions of intellectual disability. This new and specific discussion seeks to reframe the paradigm of what constituted intellectual disability at different periods in both medieval and modern times. Philosophically, and subsequently judicially, medieval intellectual disability was considered the absence of reason, representing the irrational, which contrasted the mentally disabled with the Aristotelian concept of the human being as the rational animal. Medieval terminology employed a fluidity of definitions, which highlights the constructedness of terms revolving around intellectual disability. Analyses of the culturally specific constructions of intellectual disability enhance our knowledge of the intellectual heritage underpinning current concepts of cognitive and mental pathologies.
Noxious Mechanosensation
Authors: Delmas Patrick , Korogod Sergiy Mikhailovych , Coste Bertrand 
Published: July 2018

Abstract
This article introduces a number of critical features of mechanical transduction and neuronal sensory coding, with particular reference to mechanical pain. High threshold mechanoreceptors (HTMRs) in skin are the first relay point for the transduction of noxious mechanical force into the nervous system, and their properties determine how and when nociceptive signal is relayed up to the central nervous system. The article describes the structure and physiology of the mechano-nociceptors and explains the peripheral molecular mechanisms of transduction leading to mechanical pain. In addition, this article also describes a set of computer models of HTMRs and relevant ion channels representing structural and biophysical features of the biological prototype. A better understanding of HTMRs’ function may lead to the development of novel therapeutic pathways in the treatment of chronic mechanical pain.
Using Motion Picture Films to Teach Nursing Theory in Graduate Nursing Education
Authors: Hanna Debra R. 
Published: July 2018

Abstract
Teaching strategies that use pedagogy of inquiry and contextualization are needed to ensure that nursing students will be well prepared to manage increasingly complex patient information. The rationale for using motion pictures to teach theoretical thinking is explained, and an assignment that uses motion pictures is described. Film scene assignments facilitate learning theoretical thinking skills, reading clinical situations, and understanding how theory can be useful to problem-solve ambiguous clinical situations. Motion pictures present a text-in-motion that can be studied and analyzed in a repeatable, objective, and collaborative way.
Effects of Proton Pump Inhibitor Coadministration on the Plasma Concentration of Erlotinib in Patients With Non–Small Cell Lung Cancer
Authors: Ohgami Masahiro , Kaburagi Takayuki , Kurosawa Atsuhiko , Doki Kosuke , Shiozawa Toshihiro , Hizawa Nobuyuki , Homma Masato 
Published: July 2018

Background:
Erlotinib is used for treating non–small cell lung cancer (NSCLC). Intestinal absorption of erlotinib is impaired under gastric pH elevation; therefore, coadministration of gastric acid suppressants may provide lower blood concentration of erlotinib. We investigated the effects of erlotinib coadministration with proton pump inhibitors (PPIs) and histamine H2 receptor blockers (H2RBs) on the plasma concentration of erlotinib and erlotinib-induced adverse reaction in patients with NSCLC.

Methods:
Forty-two patients receiving erlotinib therapy for NSCLC were recruited for this study. Association of adverse reactions (rash and diarrhea) with plasma concentration of erlotinib was examined. Plasma concentration-to-dose (C/D) ratios and oral clearance (CL/F), which was estimated by population pharmacokinetic analysis of plasma concentrations of erlotinib, were compared among 3 patient groups: without coadministration of gastric acid suppressants (control group), with coadministration of PPI (PPI group), and coadministration of H2RB (H2RB group).

Results:
Patients with grade ≥2 rash had higher plasma concentrations of erlotinib compared with those with grade ≤1 [1.02 (0.43–2.60) versus 0.67 (0.10–1.85) mcg/mL, P < 0.01]. The C/D ratios of erlotinib in the PPI and H2RB groups were lower than that in the control group [0.39 (0.08–0.76) and 0.48 (0.33–0.81) versus 0.51 (0.28–1.28) mcg·mL−1·mg−1·kg−1], where statistical significance was observed between PPI and control groups (P < 0.05). The population pharmacokinetic estimated oral CL/F in the PPI and H2RB groups were higher than that in the control group [5.55 (3.36–14.52) and 4.82 (2.08–6.32) versus 3.95 (2.01–10.44) L/h], where statistical significance was observed between PPI and control groups (P < 0.05).

Conclusions:
Plasma concentrations of erlotinib in patients under coadministration of gastric acid suppressants were lower than those without gastric acid suppressants through drug interaction, suppressing the intestinal absorption of erlotinib. The magnitude of this drug interaction was more pronounced in the coadministration of PPI compared with H2RB.
Successful Cochlear Implantation of a Split Electrode Array in a Patient With Far-advanced Otosclerosis Assisted by Electromagnetic Navigation: A Case Report
Authors: Dejaco Daniel , Prejban David , Fischer Natalie , Freysinger Wolfgang , Stephan Kurt , Seebacher Josef , Widmann Gerlig , Riechelmann Herbert , Schmutzhard Joachim 
Published: July 2018

Background:
Incomplete electrode insertion is frequent when implanting ossified cochleae with conventional linear electrodes. If split electrode arrays (SEA) are used, this complication occurs less frequently resulting in improved audiological performance (AP). Additional implementation of electromagnetic navigation systems (EMNS) may add additional safety to this procedure and may further improve AP. However, previously performed SEA cochlea implantations rarely implemented EMNS. The few cases reported a laborious approach with customized, three-dimensional-printed microstereotactic headframes, which limited clinical feasibility. Moreover, no postoperative AP was reported. In this case report a more feasible approach, using a commercially available EMNS, is described and postoperative AP is reported.

Patient:
A 70-year-old man with far-advanced otosclerosis was referred because of unsatisfactory speech intelligibility (monosyllabic word score of 0% at 75 dB sound pressure level) after cochlear implantation of a conventional linear electrode. Preoperative computed tomography revealed subtotal cochlear ossification and incomplete electrode insertion.

Intervention:
Four titanium screws were inserted into the petrous bone for computed tomography-based registration using an EMNS. The previous mastoidectomy was expanded, the misplaced conventional linear electrode extracted and a manual, free-handed superior cochleostomy at the level of the tendon of the tensor tympani muscle was performed. The location and course of the drill-out procedure for the SEA was planned and verified with EMNS.

Results:
Full electrode insertion for both electrode arrays of the SEA was achieved without any nerve dysfunction. Monosyllabic word score, determined 207 days after surgery, improved to 50 and 60% at 65 and 75 dB sound pressure level respectively.

Conclusion:
The implementation of EMNS in SEA cochlear implantation added additional safety to the procedure, which resulted in full electrode insertion and superior AP. Yet, outcome in cochlear implantation may vary. Larger case series to confirm this observation are required. The approach proposed for EMNS-guided SEA in this case report, using commercially available EMNS, may lead to a more frequent implementation in clinical routine due to its good clinical feasibility. Thus, larger case series may be generated.
Temporary Explant of a Transcutaneous Bone Conduction Hearing Implant for Imaging of the Pituitary Gland
Authors: Roesch Sebastian , Kugler Anton , Schlattau Alexander , Rasp Gerd 
Published: July 2018

Objective:
Clinical report on feasibility and outcome of a surgical procedure.

Patient:
Nine-year-old child, supplied with a transcutaneous bone conduction hearing implant, requiring magnetic resonance imaging of the head to exclude a tumor of the pituitary gland.

Intervention:
Temporal removal and subsequent reimplantation of the implant in a single surgical procedure.

Main Outcome Measure:
Postoperative audiometric results.

Conclusion:
Under specific clinical circumstances, temporary removal of the transcutaneous bone conduction implant described, is technically accomplishable.
Deep Learning Based Tumor Type Classification Using Gene Expression Data
Authors: Lyu Boyu , Haque Anamul 
Published: July 2018

ABSTRACTDifferential analysis occupies the most significant portion of the standard practices of RNA-Seq analysis. However, the conventional method is matching the tumor samples to the normal samples, which are both from the same tumor type. The output using such method would fail in differentiating tumor types because it lacks the knowledge from other tumor types. Pan-Cancer Atlas provides us with abundant information on 33 prevalent tumor types which could be used as prior knowledge to generate tumor-specific biomarkers. In this paper, we embedded the high dimensional RNA-Seq data into 2-D images and used a convolutional neural network to make classification of the 33 tumor types. The final accuracy we got was 95.59%, higher than another paper applying GA/KNN method on the same dataset. Based on the idea of Guided Grad Cam, as to each class, we generated significance heat-map for all the genes. By doing functional analysis on the genes with high intensities in the heat-maps, we validated that these top genes are related to tumor-specific pathways, and some of them have already been used as biomarkers, which proved the effectiveness of our method. As far as we know, we are the first to apply convolutional neural network on Pan-Cancer Atlas for classification, and we are also the first to match the significance of classification with the importance of genes. Our experiment results show that our method has a good performance and could also apply in other genomics data.
GEESE: Metabolically driven latent space learning for gene expression data
Authors: Barsacchi Marco , Terre Helena Andres , Lió Pietro 
Published: July 2018

AbstractGene expression microarrays provide a characterisation of the transcriptional activity of a particular biological sample. Their high dimensionality hampers the process of pattern recognition and extraction. Several approaches have been proposed for gleaning information about the hidden structure of the data. Among these approaches, deep generative models provide a powerful way for approximating the manifold on which the data reside.Here we develop GEESE, a deep learning based framework that provides novel insight into the manifold learning for gene expression data, employing a metabolic model to constrain the learned representation. We evaluated the proposed framework, showing its ability to capture biologically relevant features, and encoding that features in a much simpler latent space. We showed how using a metabolic model to drive the autoencoder learning process helps in achieving better generalisation to unseen data. GEESE provides a novel perspective on the problem of unsupervised learning for biological data.AvailabilitySource code of GEESE is available athttps://bitbucket.org/mbarsacchi/geese/.
Diagnosis of Osteoarthritis Subtypes with Blood Biomarkers
Authors: Zhao Kun , Lin Junxin , Wu Bingbing , Sun Guofei , An Chengrui , Paul Maswikiti Ewetse , Ouyang Hongwei 
Published: July 2018

AbstractObjectiveTo identity osteoarthritis(OA) subtypes with gene expression of peripheral blood mononuclear cells.MethodsGene expression data (GSE48556) of Genetics osteoARthritis and Progression (GARP) study was downloaded from Gene Expression Omnibus. Principal component analysis and unsupervised clustering were analyzed to identify subtypes of OA and compare major KEGG pathways and cell type enrichment using GSEA and xCell. Classification of subtypes were explored by the utilization of support vector machine.ResultsUnsupervised clustering identified two distinct OA subtypes: Group A comprised of 60 patients (56.6%) and Group B had 46 patients (43.3%). A classifier including nine genes and CD4+T cell and Regulatory T cell flow cytometry could accurately distinguish patients from each group (area under the curve of 0.99 with gene expression). Group A is typical degenerative OA with glycosaminoglycan biosynthesis and apoptosis. Group B is related to Graft versus host disease and antigen processing and presentation, which indicated OA has a new type of “Antigen processing and presentation” similarly as that of RA.ConclusionOA can be clearly classified into two distinguished subtypes with blood transcriptome, which have important significance on the development of precise OA therapeutics.
Judgments of other bias in Cochrane systematic reviews of interventions are highly inconsistent and thus hindering use and comparability of evidence
Authors: Babic Andrija , Pijuk Andela , Brázdilová Lucie , Georgieva Yuliyana , Pereira Marco António Raposo , Poklepovic Tina , Puljak Livia 
Published: July 2018

AbstractBackgroundClinical decisions are made based on Cochrane systematic reviews (CSRs), but implementation of results of evidence syntheses such as CSRs is problematic if the evidence is not prepared consistently. All systematic reviews should assess risk of bias (RoB) in included studies, and in CSRs this is done by using Cochrane RoB tool. However, the tool is not necessarily applied according to the instructions. In this study we aimed to analyze types and judgments of ‘other bias’ in the RoB tool in CSRs of interventions.MethodsWe analyzed CSRs that included randomized controlled trials (RCTs) and extracted data regarding ‘other bias’ from the RoB table and accompanying support for the judgment. We categorized different types of other bias.ResultsWe analyzed 768 CSRs that included 11369 RCTs. There were 602 (78%) CSRs that had ‘other bias’ domain in the RoB tool, and they included a total of 7811 RCTs. In the RoB table of 337 CSRs for at least one of the included trials it was indicated that no other bias was found and supporting explanations were inconsistently judged as low, unclear or high RoB. In the 524 CSRs that described various sources of other bias there were 5762 individual types of explanations which we categorized into 31 groups. The judgments of the same supporting explanations were highly inconsistent. Furthermore, we found numerous other inconsistencies in reporting of sources of other bias in CSRs.ConclusionCochrane authors mention a wide range of sources of other bias in the RoB tool and they inconsistently judge the same supporting explanations. Inconsistency in appraising risk of other bias hinders reliability and comparability of Cochrane systematic reviews. Furthermore, discrepant and erroneous judgments of bias in evidence synthesis will inevitably hinder implementation of evidence in routine clinical practice and reduce confidence of practitioners in otherwise trustworthy sources of information.
A harmonized meta-knowledgebase of clinical interpretations of cancer genomic variants
Authors: Wagner Alex H , Walsh Brian , Mayfield Georgia , Tamborero David , Sonkin Dmitriy , Krysiak Kilannin , Pons Jordi Deu , Duren Ryan P , Gao Jianjiong , McMurry Julie , Patterson Sara , Del Vecchio Fitz Catherine , Sezerman Ozman U , Warner Jeremy L , Rieke Damian T , Aittokallio Tero , Cerami Ethan , Ritter Deborah , Schriml Lynn M , Freimuth Robert R , Haendel Melissa , Raca Gordana , Madhavan Subha , Baudis Michael , Beckmann Jacques S , Dienstmann Rodrigo , Chakravarty Debyani , Li Xuan Shirley , Mockus Susan , Elemento Olivier , Schultz Nikolaus , Lopez-Bigas Nuria , Lawler Mark , Goecks Jeremy , Griffith Malachi , Griffith Obi L , Margolin Adam A ,   Variant Interpretation for Cancer Consortium
Published: July 2018

ABSTRACTPrecision oncology relies on the accurate discovery and interpretation of genomic variants to enable individualized diagnosis, prognosis, and therapy selection. We found that knowledgebases containing clinical interpretations of somatic cancer variants are highly disparate in interpretation content, structure, and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. With the cooperation of experts of the Global Alliance for Genomics and Health (GA4GH) and six prominent cancer variant knowledgebases, we developed a framework for aggregating and harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations covering 3,437 unique variants in 415 genes, 357 diseases, and 791 drugs. We demonstrated large gains in overlap between resources across variants, diseases, and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 56% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide an open and freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.
Detection ofMycobacterium lepraeDNA in soil; Multiple needles in the haystack?
Authors: Tió-Coma Maria , Wijnands Thomas , Pierneef Louise , Schilling Anna Katarina , Alam Korshed , Roy Johan Chandra , Faber William R. , Menke Henk , Pieters Toine , Stevenson Karen , Richardus Jan Hendrik , Geluk Annemieke 
Published: July 2018

AbstractBackgroundLeprosy is an infectious disease caused byMycobacterium lepraeandMycobacterium lepromatosisaffecting the skin and nerves. Despite decades of availability of adequate treatment, transmission is unabated and routes of transmission are not completely understood. Notwithstanding the general assumption that untreatedM. lepraeinfected humans represent the major source of transmission, scarce reports indicate that environmental specimens could play a role as a reservoir as well.MethodologyIn order to identify patterns of bacterial transmission, this study investigated whetherM. lepraeDNA is present in soil of regions where leprosy is endemic or areas with possible animal reservoirs (armadillos and red squirrels). Soil samples were collected in Bangladesh, Suriname and the British Isles. The presence ofM. lepraeDNA was determined by RLEP PCR andM. lepraeSNP types were further identified by Sanger sequencing of loci 1-3.ResultsM. lepraeDNA was identified in soil samples from environments inhabited by leprosy patients (Bangladesh), armadillos (Suriname) and the lepromatous Eurasian red squirrels (British Isles). In Bangladesh SNP type 1 was detected, Suriname soil contained SNP type 1 or 2, whilst SNP typing was not feasible for the British samples.ConclusionsIt is conceivable that, besides humans and animals, environmental reservoirs may play a role in transmission. Frequent, intense contact with multibacillary leprosy patients poses the highest risk of transmission, and even though the risk of environmental contamination is low, it may offer a possible explanation for the occurrence of leprosy in individuals in areas without any reported human leprosy.
Adaptive Phenotypic Plasticity for Life History and Less Fitness-Related Traits
Authors: Acasuso-Rivero Cristina , Murren Courtney J. , Schlichting Carl D. , Steiner Ulrich K. 
Published: July 2018

ABSTRACTOrganisms are faced with variable environments and one of the most common solutions to cope with such variability is phenotypic plasticity, a modification of the phenotype to the environment. These modifications influence ecological and evolutionary processes and are assumed to be adaptive. The assumption of adaptive plasticity allows to derive the prediction that the closer to fitness a trait is, the less plastic it would be. To test this hypothesis, we conducted a meta-analysis of 213 studies and measured the plasticity of each reported trait as coefficient of variation (CV). Traits were categorised according to their relationship to fitness into life-history traits (LHt) including reproduction and survival related-traits, and non-life-history traits (N-LHt) including traits related to development, metabolism and physiology, morphology and behaviour. Our results showed, unexpectedly, that although traits differed in their amounts of plasticity, trait plasticity did not correlate with its proximity to fitness. These findings were independent of taxonomic groups or environmental types assessed and raise questions about the ubiquity of adaptive plasticity. We caution about generalising the assumption that all plasticity is adaptive with respect to evolutionary and ecological population processes. More studies are needed that test the adaptive nature of plasticity, and additional theoretical explorations on adaptive and non-adaptive plasticity are encouraged.
Alzheimer’s disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines
Authors: Wohlers Inken , Schulz Colin , Kilpert Fabian , Bertram Lars 
Published: July 2018

AbstractThe role of microRNAs (miRNAs) in the pathogenesis of Alzheimer’s disease (AD) is currently extensively investigated. In this study, we assessed the potential impact of AD genetic risk variants on miRNA expression by performing large-scale bioinformatic data integration. Our analysis was based on genetic variants from three AD genome-wide association studies (GWAS). Association with miRNA expression was tested by expression quantitative trait loci (eQTL) analysis using next-generation miRNA sequencing data generated in lymphoblastoid cell lines (LCL). While, overall, we did not identify a strong effect of AD GWAS variants on miRNA expression in this cell type we highlight two notable outliers, i.e. miR-29c-5p and miR-6840-5p. MiR-29c-5p was recently reported to be involved in the regulation of BACE1 and SORL1 expression. In conclusion, despite two exceptions our large-scale assessment provides only limited support for the hypothesis that AD GWAS variants act as miRNA eQTLs.