bluuebunny/crossref_metadata_2025_split huggingface dataset:
A design framework and exemplar metrics for FAIRness
Authors: Wilkinson Mark D. , Sansone Susanna-Assunta , Schultes Erik , Doorn Peter , Bonino da Silva Santos Luiz Olavo , Dumontier Michel 
Published: November 2017

Abstract“FAIRness” - the degree to which a digital resource is Findable, Accessible, Interoperable, and Reusable - is aspirational, yet the means of reaching it may be defined by increased adherence to measurable indicators. We report on the production of a core set of semi-quantitative metrics having universal applicability for the evaluation of FAIRness, and a rubric within which additional metrics can be generated by the community. This effort is the output from a stakeholder-representative group, founded by a core of FAIR principles’ co-authors and drivers. We now seek input from the community to more broadly discuss their merit.
GABAergic deficits and schizophrenia-like behaviors in a mouse model carrying patient-derived neuroligin-2 R215H mutation
Authors: Jiang Dong-Yun , Wu Zheng , Hu Yi , Yee Siu-Pok , Chen Gong 
Published: November 2017

AbstractSchizophrenia (SCZ) is a severe mental disorder characterized by delusion, hallucination, and cognitive deficits. We have previously identified from schizophrenia patients a loss-of-function mutation Arg215 → His215 (R215H) of neuroligin 2 (NLGN2) gene, which encodes a cell adhesion molecule critical for GABAergic synapse formation and function. Here, we generated a novel transgenic mouse line with neuroligin-2 (NL2) R215H mutation, which showed a significant loss of NL2 protein, reduced GABAergic transmission, and impaired hippocampal activation. Importantly, R215H KI mice displayed anxiety-like behaviors, impaired pre-pulse inhibition (PPI), cognition deficits and abnormal stress responses, recapitulating several key aspects of schizophrenia-like behavior. Our results demonstrate a significant impact of a single point mutation NL2 R215H on brain functions, providing a novel animal model for the study of schizophrenia and neuropsychiatric disorders.
Energy saving in vision at the first synapse: The ON and OFF pathways measure temporal differences
Authors: ter Haar Romeny Bart M. 
Published: November 2017

AbstractThe inner plexiform layer (IPL) of mammalian retina has a precise bisublaminar organization in an inner on- and an outer off-layer, innervated by spatially segregated on- and off-cone bipolar cell inputs. Also, the processes of starburst amacrine cells are segregated into on and off sublaminae of the IPL. Distances between overlapping on-off pair retinal ganglion cell dendritic tree centers are markedly smaller than between on-on or off-off centers, indicating simultaneously sampling the same space. Despite dekades of research, no good model exists for the role of the on- and off pathways. Here I propose that the on- and off pairs are temporally subtracted, with one channel delayed in time, likely in a higher cortical center. The on- and off receptive fields give at every retinal location an I+ and I-signal, where I is intensity, velocity, color. Subsequent frame subtraction is a basis function of every surveillance camera for vision, and in MPEG video/sound compression. The model explains the many phenomena observed when the retinal image is stabilized. The separation of layers in the LGN fits with the notion of a time delay at higher cortical level. The directionalty observed in micro-saccades is typically perpendicular to the main edges in the scene. Precise measurement of spatio-temporal receptive field kernels shows that time is processed in the visual system as a real-time process, i.e. with a logarithmic time axis. As only contours and textures are transmitted, it is a very effective design strategy of the visual system to conserve energy, in a brain that typically uses 25 Watt and very low neuron firing frequencies. The higher visual centers perform the fill-in (inpainting) with such efficiency, that the subtraction always goes unnoticed.
ProLego: tool for extracting and visualizing topological modules in protein structures
Authors: Khan Taushif , Panday Shailesh Kumar , Ghosh Indira 
Published: November 2017

AbstractBackgroundIn protein design, correct use of topology is among the initial and most critical feature. Meticulous selection of backbone topology aids in drastically reducing the structure search space. With ProLego, we present a server application to explore the component aspect of protein structures and provide an intuitive and efficient way to scan the protein topology space.ResultWe have implemented in-house developed “topological representation” in an automated-pipeline to extract protein topology from given protein structure. Using the topology string, ProLego, compares topology against a non-redundant extensive topology database (ProLegoDB) as well as extracts constituent topological modules. The platform offers interactive topology visualization graphs.ConclusionProLego, provides an alternative but comprehensive way to scan and visualize protein topology along with an extensive database of protein topology.ProLego can be found at http://www.proteinlego.com
FamPlex: a resource for entity recognition and relationship resolution of human protein families and complexes in biomedical text mining
Authors: Bachman John A , Gyori Benjamin M , Sorger Peter K 
Published: November 2017

AbstractBackgroundFor automated reading of scientific publications to extract useful information about molecular mechanisms it is critical that genes, proteins and other entities be correctly associated with uniform identifiers, a process known as named entity linking or “grounding.” Correct grounding is essential for resolving relationships among mined information, curated interaction databases, and biological datasets. The accuracy of this process is largely dependent on the availability of machine-readable resources associating synonyms and abbreviations commonly found in biomedical literature with uniform identifiers.ResultsIn a task involving automated reading of ∼215,000 articles using the REACH event extraction software we found that grounding was disproportionately inaccurate for multi-protein families (e.g., “AKT”) and complexes with multiple subunits (e.g.”NF-κB”). To address this problem we constructed FamPlex, a manually curated resource defining protein families and complexes as they are commonly encountered in biomedical text. In FamPlex the gene-level constituents of families and complexes are defined in a flexible format allowing for multi-level, hierarchical membership. To create FamPlex, text strings corresponding to entities were identified empirically from literature and linked manually to uniform identifiers; these identifiers were also mapped to equivalent entries in multiple related databases. FamPlex also includes curated prefix and suffix patterns that improve named entity recognition and event extraction. Evaluation of REACH extractions on a test corpus of ∼54,000 articles showed that FamPlex significantly increased grounding accuracy for families and complexes (from 15% to 71%). The hierarchical organization of entities in FamPlex also made it possible to integrate otherwise unconnected mechanistic information across families, subfamilies, and individual proteins. Applications of FamPlex to the TRIPS/DRUM reading system and the Biocreative VI Bioentity Normalization Task dataset demonstrated the utility of FamPlex in other settings.ConclusionFamPlex is an effective resource for improving named entity recognition, grounding, and relationship resolution in automated reading of biomedical text. The content in FamPlex is available in both tabular and Open Biomedical Ontology formats at https://github.com/sorgerlab/famplex under the Creative Commons CC0 license and has been integrated into the TRIPS/DRUM and REACH reading systems.
Origin, evolution, and distribution of the molecular machinery for biosynthesis of sialylated lipooligosaccharide structures in Campylobacter coli
Authors: Culebro Alejandra , Machado Miguel P. , Carriço João André , Rossi Mirko 
Published: November 2017

ABSTRACTCampylobacter jejuni and Campylobacter coli are the most common cause of bacterial gastroenteritis worldwide. Additionally, C. jejuni is the most common bacterial etiological agent in the autoimmune Guillain-Barré syndrome (GBS). Ganglioside mimicry by C. jejuni lipooligosaccharide (LOS) is the triggering factor of the disease. LOS-associated genes involved in the synthesis (neuABC) and transfer of sialic acid (sialyltranferases) are essential in C. jejuni to synthesize ganglioside-like LOS. Therefore these genes have been identified as GBS markers. So far, scarce genetic evidence supports C. coli as a GBS causative agent despite being isolated from GBS patients. Here we show that genes putatively involved in sialic acid transfer are widely distributed in the C. coli population. Evidence found herein suggests that a small group of C. coli strains are very likely to express ganglioside mimics, implying that C. coli can potentially trigger GBS. C. coli also presents a larger repertoire of sialyltransferases than C. jejuni and loss of functions of some those LOS-associated genes has happened during adaptation to agriculture niche. Nevertheless, the activity of these sialyltransferases and their role in shaping C. coli population is yet to be explored.
The structure of SALM5 suggests a dimeric assembly for the presynaptic RPTP ligand recognition
Authors: Karki Sudeep , Paudel Prodeep , Sele Celeste , Shkumatov Alexander V. , Kajander Tommi 
Published: November 2017

ABSTRACTSynaptic adhesion molecules play a crucial role in the regulation of synapse development and maintenance. Recently several families of leucine rich repeat domain containing neuronal adhesion molecules have been characterized, including netrin G-ligands, LRRTMs, and the SALM family proteins. Most of these are expressed at the excitatory glutamatergic synapses, and dysfunctions of these genes are genetically linked with cognitive disorders, such as autism spectrum disorders and schizophrenia. The SALM family proteins SALM3 and SALM5, similar to SLITRKs, have been shown to bind to the presynaptic receptor protein tyrosine phosphatase (RPTP) family ligands. Here we present the 3 Å crystal structure of the SALM5 LRR-Ig domain construct, and biophysical studies that verify the crystallographic results. We show that both SALM3 and SALM5 extracellular domains form similar dimeric structures, in which the LRR domains form the dimer interface. Both proteins bind to the RPTP lg-domains with micromolar affinity. SALM3 shows a clear preference for RPTP-ligands with the meB splice insert. This is in accordance with previous results showing that the LRR domain is also required for the ligand binding. Our structural studies and sequence conservation analysis suggests a ligand binding site and mechanism for RPTP binding via the dimeric LRR domain region.
Early Archean origin of heterodimeric Photosystem I
Authors: Cardona Tanai 
Published: November 2017

AbstractWhen and how oxygenic photosynthesis originated remains controversial. Wide uncertainties exist for the earliest detection of biogenic oxygen in the geochemical record or the origin of water oxidation in ancestral lineages of the phylum Cyanobacteria. A unique trait of oxygenic photosynthesis is that the process uses a Type I reaction centre with a heterodimeric core, also known as Photosystem I, made of two distinct but homologous subunits, PsaA and PsaB. In contrast, all other known Type I reaction centres in anoxygenic phototrophs have a homodimeric core. A compelling hypothesis for the evolution of a heterodimeric Type I reaction centre is that the gene duplication that allowed the divergence of PsaA and PsaB was an adaptation to incorporate photoprotective mechanisms against the formation of reactive oxygen species, therefore occurring after the origin of water oxidation to oxygen. Here I show, using sequence comparisons and Bayesian relaxed molecular clocks that this gene duplication event may have occurred in the early Archean more than 3.4 billion years ago, long before the most recent common ancestor of crown group Cyanobacteria and the Great Oxidation Event. If the origin of water oxidation predated this gene duplication event, then that would place primordial forms of oxygenic photosynthesis at a very early stage in the evolutionary history of life.
Family‐based interventions for children and adolescents with functional somatic symptoms: a systematic review
Authors: Hulgaard Ditte , Dehlholm‐Lambertsen Gitte , Rask Charlotte Ulrikka 
Published: November 2017

AbstractFunctional somatic symptoms (FSS), defined as physical symptoms that cannot be fully explained by organic pathology, are prevalent in youngsters worldwide. When severe, they can pose a major burden on the affected individual as well as on society. FSS seem to aggregate in families, and family variables may play a key role in symptom development and perpetuation. It may, therefore, be important to work with the family when managing FSS.The aim of this systematic review was to explore and describe family‐based interventions used for children and adolescents with FSS, further to evaluate the overall quality of the research in this area. Sixteen studies were included. The psychological orientation for the applied treatment was based on systemic or cognitive behavioural therapy. Treatment focused on family illness beliefs and on a shift away from somatic symptom attribution to alternative explanations that were shaped by the psychological orientation of the applied treatment.Practitioner points

Family influences are significant for functional somatic symptoms in youngsters

Family intervention may be a relevant treatment approach for youngsters with functional somatic symptoms

Family‐based psychotherapy for youngsters with functional somatic symptoms is mainly based on cognitive behavioural therapy or on systemic family therapy

Illness beliefs of the child/adolescent as well as illness beliefs of the family as a whole could be important treatment targets in young people with functional somatic symptoms
Analysis of differential proteins in two different wing‐types of female Nilaparvata lugens
Authors: Liang An‐Wen , Liu Ting‐Ting , Liang Zi‐Qiang , Wang Fang‐Hai 
Published: November 2017

AbstractNilaparvata lugens (stal) is a rice pest and contains long‐winged and short‐winged varieties, called the wing differentiation. This study compared the protein profiles of the two wing‐types in females and two wing‐disc types 5th‐instar females by two‐dimensional electrophoresis analysis. We detected 172 and 174 protein spots in adults and 5th‐instar nymphs, respectively. The number of proteins with higher content in the long‐winged (disc) individuals is much more than that in the short‐winged (disc) individuals. A total of 32 differential protein spots were found, of which 20 were successfully identified. Their main function is about catabolic process, fiber and nucleoside binding, and they constitute 52 protein–protein interactions, which is around the glycolysis as the core. These results enrich the research on the protein Level in wing development, and provide more references for future studies.
Precise Quantitative Assessment of the Clinical Performances of Two High‐Flux Polysulfone Hemodialyzers in Hemodialysis: Validation of a Blood‐Based Simple Kinetic Model Versus Direct Dialysis Quantification
Authors: Lim Paik‐Seong , Lin Yuyu , Chen Minfeng , Xu Xiaoqi , Shi Yun , Bowry Sudhir , Canaud Bernard 
Published: November 2017

AbstractHighly permeable dialysis membranes with better design filters have contributed to improved solute removal and dialysis efficacy. However, solute membrane permeability needs to be well controlled to avoid increased loss of albumin that is considered to be detrimental for dialysis patients. A novel high‐flux dialyzer type (FX CorDiax; Fresenius Medical Care) incorporating an advanced polysulfone membrane modified with nano‐controlled spinning technology to enhance the elimination of a broader spectrum of uremic toxins has been released. The aim of this study was to compare in the clinical setting two dialyzer types having the same surface area, the current (FX dialyzer) and the new dialyzer generation (FX CorDiax), with respect to solute removal capacity over a broad spectrum of markers, including assessment of albumin loss based on a direct dialysis quantification method. We performed a crossover study following an A1‐B‐A2 design involving 10 patients. Phase A1 was 1 week of thrice‐weekly bicarbonate hemodialysis with the FX dialyzer, 4 h per treatment; phase B was performed with a similar treatment regimen but with a new FX CorDiax dialyzer and finally the phase A2 was repeated with FX dialyzer as the former phase. Solute removal markers of interest were assessed from blood samples taken before and after treatment and from total spent dialysate collection (direct dialysis quantification) permitting a mass transfer calculation (mg/session into total spent dialysate/ultrafiltrate). On the blood side, there were no significant differences in the solute percent reduction between FX CorDiax 80 and FX 80. On the dialysate side, no difference was observed regarding eliminated mass of different solutes including β2‐microglobulin (143.1 ± 33.6 vs. 138.3 ± 41.9 mg, P = 0.8), while the solute mass removal of total protein (1.65 ± 0.51 vs. 2.14 ± 0.75 g, P = 0.04), and albumin (0.41 ± 0.21 vs. 1.22 ± 0.51 g, P < 0.001) were significantly less for FX CorDiax 80 compared to the FX 80 dialyzer. The results of this cross‐over study indicate that the new FX CorDiax dialyzer has highly effective removal of middle molecules, without any concomitant increase in total protein and albumin loss. The clinical relevance and potential benefit of this finding needs to be determined.
Sofosbuvir and velpatasvir with or without voxilaprevir in direct‐acting antiviral‐naïve chronic hepatitis C: patient‐reported outcomes from POLARIS 2 and 3
Authors: Younossi Z. M. , Stepanova M. , Jacobson I. M. , Asselah T. , Gane E. J. , Lawitz E. , Foster G. R. , Roberts S. K. , Thompson A. J. , Willems B. E. , Welzel T. M. , Pearlman B. , Younossi I. , Racila A. , Henry L. 
Published: November 2017

SummaryBackgroundChronic hepatitis C infection leads to impairment of patient‐reported outcomes (PROs). Treatment with direct‐acting antiviral regimens results in short‐ and long‐term improvement of these outcomes.AimTo assess PROs in patients treated with a newly developed direct‐acting antiviral, a fixed‐dose combination of sofosbuvir/velpatasvir (SOF/VEL) with/without voxilaprevir (VOX).MethodsThe PRO data were collected from participants of POLARIS‐2 and POLARIS‐3 clinical trials (DAA‐naïve, all HCV genotypes). Participants self‐administered SF‐36v2, FACIT‐F, CLDQ‐HCV and WPAI:SHP instruments at baseline, during treatment, and in follow‐up.ResultsOf 1160 patients, 611 received SOF/VEL/VOX and 549 received SOF/VEL (52.8 ± 11.0 years, 55.9% male, 75.4% treatment‐naïve, 33.9% cirrhotic). The sustained viral response at 12 weeks (SVR12) rates were 95%‐98%. During treatment, improvements in most PRO scores were significant (all but one P < .01) and ranged from, on average, +2.3 to +15.0 points (on a 0‐100 scale) by the end of treatment. These improvements were similar between SOF/VEL/VOX and SOF/VEL arms (all P > .05). After treatment discontinuation, patients treated with both regimens achieved significant and clinically meaningful PRO gains (+2.7 to +16.7 by post‐treatment week 12, +3.9 to +20.1 by post‐treatment week 24; all but one P < .001). Multivariate analysis showed that depression, anxiety and cirrhosis were the most consistent independent predictors of PRO impairment while no association of PROs with the treatment regimen choice was found (all P > .05).ConclusionsThe pan‐genotypic regimens with SOF/VEL with or without VOX not only have excellent efficacy and safety, but also significantly positively impact patients’ experience both during treatment and after achieving sustained virologic response in DAA‐naïve patients with HCV.
Tumor invasion to the arteries feeding the gallbladder as a novel risk factor for cholecystitis after metallic stent placement in distal malignant biliary obstruction
Authors: Sogabe Yuko , Kodama Yuzo , Honjo Hajime , Aoyama Ikuo , Muramoto Yuya , Koga Eri , Yanaidani Takafumi , Kawai Munenori , Yoshikawa Teppei , Matsumoto Shimpei , Matsumoto Astushi , Mori Yoshiharu , Ono Chikage , Nishida Miyu , Nishida Yoshihiro , Mikami Takao , Matsunaga Yasuhiro , Miyamoto Yukiko , Kitami Motoya , Nishikawa Koji , Kondo Masahiko , Miyake Naoki , Kawanami Chiharu , Seno Hiroshi 
Published: November 2017

Background and AimCholecystitis is a major complication after self‐expandable metallic stent (SEMS) placement for malignant biliary obstruction. Ischemia is one of the risk factors for cholecystitis, but little is known about the influence of tumor invasion to the feeding artery of the gallbladder on the onset of cholecystitis after SEMS placement. The aim of the present study was to identify risk factors for cholecystitis after SEMS placement.MethodsIncidence and nine predictive factors of cholecystitis were retrospectively evaluated in 107 patients who underwent SEMS placement for unresectable distal malignant biliary obstruction at Kyoto University Hospital and Otsu Red Cross Hospital between January 2012 and June 2016.ResultsCholecystitis occurred in 13 of 107 patients (12.1%) after SEMS placement during the median follow‐up period of 262 days. Univariate analyses showed that tumor invasion to the feeding artery of the gallbladder and tumor involvement to the orifice of the cystic duct were significant predictors of cholecystitis (P = 0.001 and P < 0.001). Multivariate analysis confirmed that these two factors were significant and independent risks for cholecystitis with odds ratios of 22.13 (95% CI, 3.57–137.18; P = 0.001) and 25.26 (95% CI, 4.12–154.98; P < 0.001), respectively.ConclusionsThis study showed for the first time that tumor invasion to the feeding artery of the gallbladder as well as tumor involvement to the orifice of the cystic duct are independent risk factors for cholecystitis after SEMS placement.
Pediatric acute kidney injury induced by concomitant vancomycin and piperacillin–tazobactam
Authors: Abouelkheir Manal , Alsubaie Sarah 
Published: November 2017

AbstractBackgroundVancomycin is very commonly used in combination with piperacillin–tazobactam (PTZ) as the initial empiric treatment for moderate–severe infection, whenever coverage for both methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa is required. The combination of vancomycin and PTZ in adults has recently been reported to significantly increase the risk of acute kidney injury (AKI) relative to vancomycin monotherapy; such reports in pediatrics, however, are sparse.MethodsA retrospective chart review was conducted of pediatric patients, aged 0–14 years, who were admitted to the general wards or intensive care unit and developed AKI after receiving vancomycin and PTZ concomitantly for >48 h. AKI is defined as a decrease in estimated glomerular filtration rate ≥50% from baseline. Cases were identified by reviewing the Adverse Drug Reaction program database at King Saud University Medical City in Saudi Arabia from January 2015 to June 2016.ResultsEight children admitted to the present hospital and who received concomitant vancomycin and PTZ treatment for pneumonia (n = 7) or febrile neutropenia (n = 1) developed drug‐induced nephrotoxicity. Drug Interaction Probability Scale (DIPS) score for causation assessment was 9 in all cases (highly probable).ConclusionCaution in utilizing the combination of vancomycin and PTZ is warranted in pediatric patients. Health‐care professionals should be vigilant if this combination is to be initiated, and ensure close monitoring of renal function. Antibiotic therapy de‐escalation should be considered as soon as culture results are available.