bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orthologue chemical space and its influence on target prediction
Authors: Mervin Lewis H , Bulusu Krishna C , Kalash Leen , Afzal Avid M , Svensson Fredrik , Firth Mike A , Barrett Ian , Engkvist Ola , Bender Andreas 
Published: August 2017

Abstract

Motivation
In silico approaches often fail to utilize bioactivity data available for orthologous targets due to insufficient evidence highlighting the benefit for such an approach. Deeper investigation into orthologue chemical space and its influence toward expanding compound and target coverage is necessary to improve the confidence in this practice.

Results
Here we present analysis of the orthologue chemical space in ChEMBL and PubChem and its impact on target prediction. We highlight the number of conflicting bioactivities between human and orthologues is low and annotations are overall compatible. Chemical space analysis shows orthologues are chemically dissimilar to human with high intra-group similarity, suggesting they could effectively extend the chemical space modelled. Based on these observations, we show the benefit of orthologue inclusion in terms of novel target coverage. We also benchmarked predictive models using a time-series split and also using bioactivities from Chemistry Connect and HTS data available at AstraZeneca, showing that orthologue bioactivity inclusion statistically improved performance.

Availability and implementation
Orthologue-based bioactivity prediction and the compound training set are available at www.github.com/lhm30/PIDGINv2.

Supplementary information
Supplementary data are available at Bioinformatics online.
Deep machine learning provides state-of-the-art performance in image-based plant phenotyping
Authors: Pound Michael P. , Atkinson Jonathan A. , Townsend Alexandra J. , Wilson Michael H. , Griffiths Marcus , Jackson Aaron S. , Bulat Adrian , Tzimiropoulos Georgios , Wells Darren M. , Murchie Erik H. , Pridmore Tony P. , French Andrew P. 
Published: August 2017

Abstract
In plant phenotyping, it has become important to be able to measure many features on large image sets in order to aid genetic discovery. The size of the datasets, now often captured robotically, often precludes manual inspection, hence the motivation for finding a fully automated approach. Deep learning is an emerging field that promises unparalleled results on many data analysis problems. Building on artificial neural networks, deep approaches have many more hidden layers in the network, and hence have greater discriminative and predictive power. We demonstrate the use of such approaches as part of a plant phenotyping pipeline. We show the success offered by such techniques when applied to the challenging problem of image-based plant phenotyping and demonstrate state-of-the-art results (&gt;97% accuracy) for root and shoot feature identification and localization. We use fully automated trait identification using deep learning to identify quantitative trait loci in root architecture datasets. The majority (12 out of 14) of manually identified quantitative trait loci were also discovered using our automated approach based on deep learning detection to locate plant features. We have shown deep learning–based phenotyping to have very good detection and localization accuracy in validation and testing image sets. We have shown that such features can be used to derive meaningful biological traits, which in turn can be used in quantitative trait loci discovery pipelines. This process can be completely automated. We predict a paradigm shift in image-based phenotyping bought about by such deep learning approaches, given sufficient training sets.
Late Arterial Thrombosis after Microvascular Head and Neck Reconstruction due to Combined Factors of Pedicle Artery Loop and Submandibular Gland Swelling
Authors: Kagaya Yu , Arikawa Masaki , Miyamoto Shimpei 
Published: August 2017

Summary:
Late arterial thrombosis of a free flap is rare and usually unsalvageable because it is hard to detect. We herein report 2 cases of arterial thrombosis of a free flap after microvascular head and neck reconstruction due to the combined factors of pedicle artery loop and compression by a swollen submandibular gland, the occurrence of thrombosis in both of which was > 72 hours after the operation. In case 1, the arterial thrombosis was undetectable, and it was too late for a successful take-back operation, so the flap was lost. However, we applied the lessons learned from case 1 and were able to detect the late arterial thrombosis of case 2 at an early stage; we subsequently salvaged the flap successfully. During the take-back operation in both cases, it was found that the submandibular gland became swollen and compressed the pedicle artery, which then became occluded due to a steep loop formation. Postoperative swelling of the submandibular gland can sometimes compress the vascular pedicle, and complete occlusion of the pedicle artery may occur when it is looped. Meticulous care concerning the geometry of the vascular pedicle is required to avoid such complications.
Group Enrollment and Open Gym Format Decreases Cardiac Rehabilitation Wait Times
Authors: Bachmann Justin M. , Klint Zachary W. , Jagoda Allison M. , McNatt Jeremy K. , Abney Lesa R. , Huang Shi , Liddle David G. , Frontera Walter R. , Freiberg Matthew S. 
Published: August 2017

Purpose:
Wait times for the first cardiac rehabilitation (CR) session are inversely related to CR participation rates. We hypothesized that changing from individually scheduled appointments to a group enrollment and open gym format, in which patients were enrolled during group intake sessions and could arrive for subsequent CR sessions any time during open gym periods, would decrease wait times.

Methods:
A total of 603 patients enrolled in CR at Vanderbilt University Medical Center from July 2012 to December 2014 were included in the study. We evaluated the effect of changing to a group enrollment and open gym format after adjusting for referral diagnosis, insurance status, seasonality, and other factors. We compared outcomes, including exercise capacity and quality of life, between the 2 groups.

Results:
Patients in the group enrollment and open gym format had significantly lower average wait times than those receiving individual appointments (14.9 vs 19.5 days, P < .001). After multivariable adjustment, the new CR delivery model was associated with a 22% (3.7 days) decrease in average wait times (95% CI, 1.9-5.6, P < .001). Patients completing CR had equally beneficial changes in 6-minute walk distance and Patient Health Questionnaire scores between the 2 groups, although there was no significant difference in participation rates or the number of sessions attended.

Conclusions:
Implementation of a group enrollment and open gym format was associated with a significant decrease in wait times for first CR sessions. This CR delivery model may be an option for programs seeking to decrease wait times.
A Child With Accidental Overdose and Intramuscular Administration of Bacillus Calmette-Guérin Vaccine
Authors: Çağlar İlknur , Düzgöl Mine , Kara Ahu , Bayram Süleyman Nuri , Apa Hurşit , Devrim İlker 
Published: August 2017

Abstract
Inadvertent bacillus Calmette-Guérin can cause complications. This report presents a 17-month-old boy with inadvertent, high-dose intramuscular bacillus Calmette-Guérin vaccination. Uniquely, our patient had abscess despite isoniazid prophylaxis. He had complete recovery with antimycobacterial treatment. Because there is no consensus about the management of these cases, close follow-up and prompt initiation of antimycobacterial treatment is essential in case of development of new symptoms.
Angioinvasion by Cunninghamella as a Cause of Anterior Spinal Artery Syndrome in an Immunocompromised Patient
Authors: Engskow Danielle G. , Nanjappa Sowmya , Tran Nam D. , Sandin Ramon L. , Greene John N. 
Published: August 2017

Abstract

Cunninghamella bertholletiae is an opportunistic fungi species in the order Mucorales that almost exclusively affects immunocompromised hosts. It is highly invasive and is well known for angioinvasion of surrounding vasculature. We describe a case of pulmonary Cunninghamella infection with dissemination and invasion of the anterior spinal artery causing anterior spinal artery syndrome.
Master student's application of evidence-based knowledge and skills in Swedish healthcare practice
Authors: Ekvall Hansson Eva , Carlsson Gunilla , Fänge Agneta Malmgren 
Published: August 2017

ABSTRACT

Aim:
To investigate the application of evidence-based knowledge and skills in everyday healthcare practice among healthcare personnel attending a course in evidence-based practice (EBP) at the master's level.

Methods:
In this cross-sectional study, an evaluation of the use of instrumental, conceptual and persuasive research was performed among students attending a master's course in EBP at Lund University. Seven questions from the validated questionnaire in the Longitudinal Analysis of Nursing Education project were used. The questionnaire was distributed among 21 students at the first lecture in the course (the group before the course). Students who had participated in the course 1 (n = 15) and 2 (n = 13) years earlier received the questionnaire by ordinary mail (the group after the course).

Results:
The current study revealed that the majority of the students used research in their daily healthcare practice. However, the extent and type of use varied. There were differences in research use between the ‘before’ and ‘after’ groups. More specifically, the students in the group responding after the course were significantly more prone to use research in practice than the students responding before the course (P = 0.01 and 0.04).

Conclusion:
An EBP course offered to master's degree students provides enhancement of evidence-based knowledge and skills, and stimulates research use in healthcare practice.
Differential spatiotemporal representations along the hippocampal long axis in humans
Authors: Brunec Iva K. , Bellana Buddhika , Ozubko Jason D. , Man Vincent , Robin Jessica , Liu Zhong-Xu , Grady Cheryl , Rosenbaum R. Shayna , Winocur Gordon , Barense Morgan D. , Moscovitch Morris 
Published: August 2017

AbstractIncreased place field size and signal autocorrelation along the dorsoventral hippocampal axis in rodents are considered a fundamental aspect of hippocampal organization, yet such evidence is lacking in humans. Using fMRI, we report corresponding evidence of increasing neural similarity from posterior to anterior hippocampus (dorsoventral homologues) in humans. These findings help account for observed shifting in representational granularity, from global context (anterior) to local details (posterior), along the hippocampal axis.
Pan-cancer analysis of whole genomes reveals driver rearrangements promoted by LINE-1 retrotransposition in human tumours
Authors: Rodriguez-Martin Bernardo , Alvarez Eva G. , Baez-Ortega Adrian , Zamora Jorge , Supek Fran , Demeulemeester Jonas , Santamarina Martin , Ju Young Seok , Temes Javier , Garcia-Souto Daniel , Detering Harald , Li Yilong , Rodriguez-Castro Jorge , Dueso-Barroso Ana , Bruzos Alicia L. , Dentro Stefan C. , Blanco Miguel G. , Contino Gianmarco , Ardeljan Daniel , Tojo Marta , Roberts Nicola D. , Zumalave Sonia , Edwards Paul A. W. , Weischenfeldt Joachim , Puiggros Montserrat , Chong Zechen , Chen Ken , Lee Eunjung Alice , Wala Jeremiah A. , Raine Keiran , Butler Adam , Waszak Sebastian M. , Navarro Fabio C. P. , Schumacher Steven E. , Monlong Jean , Maura Francesco , Bolli Niccolo , Bourque Guillaume , Gerstein Mark , Park Peter J. , Wedge David , Beroukhim Rameen , Torrents David , Korbel Jan O. , Martincorena Inigo , Fitzgerald Rebecca C. , Loo Peter Van , Kazazian Haig H. , Burns Kathleen H. , Campbell Peter J. , Tubio Jose M. C. ,   on behalf of the PCAWG Structural Variation Working Group,   the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: August 2017

AbstractAbout half of all cancers have somatic integrations of retrotransposons. To characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 37 histological cancer subtypes. We identified 19,166 somatically acquired retrotransposition events, affecting 35% of samples, and spanning a range of event types. L1 insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, sometimes removing tumour suppressor genes, as well as inducing complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications in the development of human tumours.
Coexistence of multiple endemic and pandemic lineages of the rice blast pathogen
Authors: Gladieux Pierre , Ravel Sébastien , Rieux Adrien , Cros-Arteil Sandrine , Adreit Henri , Milazzo Joëlle , Thierry Maud , Fournier Elisabeth , Terauchi Ryohei , Tharreau Didier 
Published: August 2017

AbstractThe rice blast fungusMagnaporthe oryzae(syn.Pyricularia oryzae) is both a threat to global food security and a model for plant pathology. Molecular pathologists need an accurate understanding of the origins and line of descent ofM. oryzaepopulations, to identify the genetic and functional bases of pathogen adaptation, and to guide the development of more effective control strategies. We used a whole-genome sequence analysis of samples from different times and places to infer details about the genetic makeup ofM. oryzaefrom a global collection of isolates. Analyses of population structure identified six lineages withinM. oryzae, including two pandemic on japonica and indica rice, respectively, and four lineages with more restricted distributions. Tip-dating calibration indicated thatM. oryzaelineages separated about a millenium ago, long after the initial domestication of rice. The major lineage endemic to continental Southeast Asia displayed signatures of sexual recombination and evidence of DNA acquisition from multiple lineages. Tests for weak natural selection revealed that the pandemic spread of clonal lineages entailed an evolutionary ‘cost’, in terms of the accumulation of deleterious mutations. Our findings reveal the coexistence of multiple endemic and pandemic lineages with contrasting population and genetic characteristics within a widely distributed pathogen.ImportanceThe rice blast fungusMagnaporthe oryzae(syn.Pyricularia oryzae) is a textbook example of a rapidly adapting pathogen, and is responsible for one of the most damaging diseases of rice. Improvements in our understanding ofMagnaporthe oryzaediversity and evolution are required, to guide the development of more effective control strategies. We used genome sequencing data for samples from around the world to infer the evolutionary history ofM. oryzae.We found thatM. oryzaediversified about a thousand years ago ago, separating into six main lineages: two pandemic on japonica and indica rice, respectively, and four with more restricted distributions. We also found that a lineage endemic to continental Southeast Asia displayed signatures of sexual recombination and the acquisition of genetic material from multiple lineages. This work provides a population-level genomic framework for defining molecular markers for the control of rice blast and investigations of the molecular basis of differences in pathogenicity betweenM. oryzaelineages.
Computer Simulations Predict High Structural Heterogeneity of Functional State of NMDA Receptors
Authors: Sinitskiy Anton V. , Pande Vijay S. 
Published: August 2017

AbstractIt is unclear how the known atomic structures of neuronal NMDA receptors (NMDARs) relate to the functional states of NMDARs inferred from electrophysiological recordings. We address this problem by all-atom computer simulations, a method successfully applied in the past to much smaller biomolecules. Our simulations predict that four ‘non-active’ cryoEM structures of NMDARs rapidly interconvert on submicrosecond timescales, and therefore, correspond to the same functional state of the receptor.
Alpha activity in the ventral and dorsal visual stream controls information flow during working memory
Authors: Leszczynski Marcin , Fell Juergen , Jensen Ole , Axmacher Nikolai 
Published: August 2017

AbstractThe electrophysiological mechanisms underlying working memory maintenance of information in the ventral and dorsal visual stream (VVS, DVS) remain elusive. Here we used electrocorticography recordings covering VVS, DVS and prefrontal cortex (PFC) in epilepsy patients while they were performing a delayed match-to-sample task. The experimental conditions (face identity, orientation) were designed to engage either the VVS or DVS. Alpha power was reduced in the VVS during maintenance of face identity and in the DVS during maintenance of spatial orientation of the very same stimuli. The phase of alpha oscillations modulated broadband high-frequency activity (BHA) in both regions. Interestingly, BHA occurred across broader alpha phase ranges when task-relevant information was maintained, putatively reflecting longer excitable “duty cycles”. Our findings support a model in which the VVS and DVS are recruited by the PFC via selective reduction of alpha power. As a result, excitable duty cycles in the relevant area are extended.
Chick cranial neural crest cells migrate by progressively refining the polarity of their protrusions
Authors: Genuth Miriam A. , Allen Christopher D.C. , Mikawa Takashi , Weiner Orion D. 
Published: August 2017

SummaryIn vivoquantitative imaging reveals that chick cranial neural crest cells throughout the migratory stream are morphologically polarized and migrate by progressively refining the polarity of their protrusions.AbstractTo move directionally, cells can bias the generation of protrusions or select among randomly generated protrusions. Here we use 3D two-photon imaging of chick branchial arch 2 directed neural crest cells to probe how these mechanisms contribute to directed movement, whether a subset or the majority of cells polarize during movement, and how the different classes of protrusions relate to one another. We find that cells throughout the stream are morphologically polarized along the direction of overall stream movement and that there is a progressive sharpening of the morphological polarity program. Neural crest cells have weak spatial biases in filopodia generation and lifetime. Local bursts of filopodial generation precede the generation of larger protrusions. These larger protrusions are more spatially biased than the filopodia, and the subset of protrusions that power motility are the most polarized of all. Orientation rather than position is the best correlate of the protrusions that are selected for cell movement. This progressive polarity refinement strategy may enable neural crest cells to efficiently explore their environment and migrate accurately in the face of noisy guidance cues.
Insights into autophagosome biogenesis from structural and biochemical analyses of the ATG2AWIPI4 complex
Authors: Chowdhury Saikat , Otomo Chinatsu , Leitner Alexander , Ohashi Kazuto , Aebersold Ruedi , Lander Gabriel C. , Otomo Takanori 
Published: August 2017

AbstractAutophagy is an enigmatic cellular process in which double-membrane compartments, called autophagosomes, formde novoadjacent to the endoplasmic reticulum (ER) and package cytoplasmic contents for delivery to lysosomes. Expansion of the precursor membrane phagophore requires autophagy-related 2 (ATG2), which localizes to the phosphatidylinositol-3-phosphate (PI3P)-enriched ER-phagophore junction. We combined single-particle electron microscopy, chemical cross-linking coupled with mass spectrometry, and biochemical analyses to characterize human ATG2A in complex with the PI3P effector WIPI4. ATG2A is a rod-shaped protein that can bridge neighboring vesicles through interactions at each of its tips. WIPI4 binds to one of the tips, enabling the ATG2A-WIPI4 complex to tether a PI3P-containing vesicle to another PI3P-free vesicle. These data suggest that the ATG2A-WIPI4 complex mediates ER-phagophore association and/or tethers vesicles to the ER-phagophore junction, establishing the required organization for phagophore expansion via the transfer of lipid membranes from the ER and/or the vesicles to the phagophore.
Propagation of Beta/Gamma Rhythms in the Cortico-Basal Ganglia Circuits of the Parkinsonian Rat
Authors: West Timothy O. , Berthouze Luc , Halliday David M. , Litvak Vladimir , Sharott Andrew , Magill Peter J. , Farmer Simon F. 
Published: August 2017

AbstractSome motor impairments associated with Parkinson’s disease are thought to arise from pathological activity in the neuronal networks formed by the basal ganglia (BG) and motor cortex. To evaluate several hypotheses proposed to explain the emergence of pathological oscillations in Parkinsonism, we investigated changes to the directed connectivity in these networks following dopamine depletion. We recorded local field potentials in the cortex and basal ganglia of anesthetized rats rendered Parkinsonian by injection of 6-hydroxydopamine (6-OHDA), with dopamine-intact rats as controls. We performed systematic analyses of the networks using a novel tool for estimation of directed neural interactions, as well as a conditioned variant which permits the analysis of the dependence of a connection upon a third reference signal. We find evidence of the dopamine dependency of both low beta (14-20 Hz) and high beta/low gamma (20-40 Hz) directed interactions within the BG and cortico-BG networks. Notably, 6-OHDA lesions were associated with enhancement of the cortical “hyperdirect” connection to the subthalamic nucleus (STN), as well the STN’s feedback to the cortex and striatum. We find beta synchronization to be robust to conditioning using signals from any one structure. Conversely, we find that high beta/gamma drive from the cortex to subcortical regions is weakened by 6-OHDA lesions and is susceptible to conditioning. Furthermore, we provide evidence that gamma is routed from striatum in a pathway that is independent of STN. These results further inform our understanding of the substrates for pathological rhythms in salient brain networks in Parkinsonism.New & NoteworthyWe present a novel analysis of electrophysiological recordings in the cortico-basal ganglia network with the aims of evaluating several hypotheses concerning the origins of abnormal brain rhythms associated with Parkinson’s disease. We present evidence for changes in the directed connections within the network following chronic dopamine depletion in rodents. These findings speak to the plausibility of a “short-circuiting” of the network that gives rise to the conditions from which pathological synchronization may arise.