bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Naturalistic Evaluation of Change in Antidepressant Prescription in Patients With Affective and Anxiety Disorders in a Tertiary Care Hospital of India
Authors: Patil Amol , Sahoo Swapnajeet , Garg Gaurav , Grover Sandeep 
Published: December 2017

Abstract

Background
Although many studies have evaluated prescription patterns, there is lack of information on the choice of antidepressants among patients who do not respond antidepressants. Similarly, information on switching strategies is also limited. This naturalistic study aimed to evaluate the switching strategies and preferred antidepressants by the psychiatrists among patients who do not respond to or who are not able to tolerate an antidepressant.

Methods
A cross-sectional observational study design was followed. Patients diagnosed with affective and anxiety disorders, who were recommended a change in antidepressant, were recruited. Details of antidepressant before switching, antidepressants considered at the time of switching, coprescription advised at the time of switching, reasons considered for switching, and strategy advised at the time of switching were noted down.

Results
A total of 102 patients were recruited. The most common change strategy was selective serotonin reuptake inhibitor (SSRI) to a serotonin norepinephrine reuptake inhibitor (SNRI) (N = 42; 41.17%), and this was followed by SSRI to SSRI (N = 18; 17.64%) and SNRI to SSRI (N = 10; 9.8%). In majority of the patients (N = 79; 77.45%) cross-taper of older antidepressant with gradual increase in dose of newer antidepressants was followed. About 44.1% of the patients were on adjuvant medications at the time of considering change in antidepressants, and 37.25% of the patients were additionally started on some adjuvant medications during the change of antidepressants.

Conclusions
The present study suggests that the most common strategy followed during change of antidepressant is from SSRI to SNRI and this is followed by SSRI to SSRI and SNRI to SSRI. Cross-taper switching strategy along with the use of adjuvant medications like benzodiazepines during the process of switching is most commonly followed.
Effect of Aromatherapy Massage on Chemotherapy-Induced Peripheral Neuropathic Pain and Fatigue in Patients Receiving Oxaliplatin
Authors: Izgu Nur , Ozdemir Leyla , Bugdayci Basal Fatma 
Published: December 2017

Background
Patients receiving oxaliplatin may experience peripheral neuropathic pain and fatigue. Aromatherapy massage, a nonpharmacological method, may help to control these symptoms.

Objective
The aim of this open-label, parallel-group, quasi–randomized controlled pilot study was to investigate the effect of aromatherapy massage on chemotherapy-induced peripheral neuropathic pain and fatigue in patients receiving oxaliplatin.

Methods
Stratified randomization was used to allocate 46 patients to 2 groups: intervention (n = 22) and control (n = 24). Between week 1 and week 6, participants in the intervention group (IG) received aromatherapy massage 3 times a week. There was no intervention in weeks 7 and 8. The control group (CG) received routine care. Neuropathic pain was identified using the Douleur Neuropathique 4 Questions; severity of painful paresthesia was assessed with the numerical rating scale; fatigue severity was identified with the Piper Fatigue Scale.

Results
At week 6, the rate of neuropathic pain was significantly lower in the IG, when compared with the CG. The severity of painful paresthesia based on numerical rating scale in the IG was significantly lower than that in the CG at weeks 2, 4, and 6. At week 8, fatigue severity in the IG was significantly lower when compared with CG (P < .05).

Conclusion
Aromatherapy massage may be useful in the management of chemotherapy-induced peripheral neuropathic pain and fatigue.

Implications for Practice
This pilot study suggests that aromatherapy massage may be useful to relieve neuropathic pain and fatigue. However, there is a need for further clinical trials to validate the results of this study.
Subjective inflation of color saturation in the periphery under temporal overload
Authors: Rajananda Sivananda , A.K. Peters Megan , Lau Hakwan , Odegaard Brian 
Published: December 2017

AbstractA long-standing puzzle in perception concerns the subjective impression of vivid color experience in the periphery. While peripheral color processing is not entirely insensitive, the subjective vividness seems unsupported by the relative paucity of representation in the periphery. Inspired by the flashed face distortion effect, in which peripheral faces are perceived as somewhat exaggerated or distorted when they are preceded by flashes of other faces in the same location, we attempted to create an equivalent illusion in the domain of color. The hypothesis is that under temporal overload, patches of colorful dots may be perceived as more exaggerated in terms of saturation. We confirmed this hypothesis with the observation of a significant effect of modest magnitude, which was replicated in a second experiment. These results suggest that subjective inflation of perceived color saturation does occur in the periphery, when the perceptual system is sufficiently occupied temporally and spatially. We discuss the relationship between the observed effects with previous findings of liberal detection biases in the unattended periphery.
Interleukin-4 restores neurogenic plasticity of the primary human neural stem cells through suppression of Kynurenic acid production upon Amyloid-beta42 toxicity
Authors: Papadimitriou Christos , Celikkaya Hilal , Cosacak Mehmet Ilyas , Mashkaryan Violeta , Bhattarai Prabesh , Lin Weilin , Thomas Alvin Kuriakose , Zhang Yixin , Freudenberg Uwe , Werner Carsten , Kizil Caghan 
Published: December 2017

AbstractThe immune response is an important determinant of the plasticity and neurogenic capacity of neural stem cells (NSCs) upon amyloid-beta42 (Aβ42) toxicity in Alzheimer’s disease (AD). However, the direct effects of individual immuno-modulatory effectors on NSC plasticity remain to be elucidated and are the motivation for reductionist tissue-mimetic culture experiments. Using starPEG-Heparin hydrogel system that provides a defined 3D cell-instructive neuro-microenvironment culture system, sustains high levels of proliferative and neurogenic activity of human NSCs, and recapitulates the fundamental pathological consequences of Amyloid toxicity upon Aβ42 administration, we found that the anti-inflammatory cytokine interleukin-4 (IL4) restores the plasticity and neurogenic capacity of NSCs by suppressing the Aβ42-induced kynurenic acid-producing enzyme kynurenine aminotransferase 2 (KAT2), which we also found to be upregulated in the brains of the AD model, APP/PS1dE9 mouse. Our transcriptome analyses showed that IL4 treatment restores the expression levels of NSC and cortical subtype markers. Thus, our dissective neuro-microenvironment culture revealed IL4-mediated neuroinflammatory crosstalk for human NSC plasticity and predicted a new mechanistic target for therapeutic intervention in AD.
Fibroblast Growth Factor 2 lethally sensitizes cancer cells to stress-targeted therapeutic inhibitors
Authors: Dias Matheus H. , Fonseca Cecília S , Zeidler Julianna D. , Albuquerque Layra L. , da Silva Marcelo S. , Cararo-Lopes Eduardo , Reis Marcelo S. , Noël Vincent , Prior Ian A. , Armelin Hugo A. 
Published: December 2017

ABSTRACTIn malignant transformation, cellular stress response pathways are dynamically mobilized to counterbalance oncogenic activity, keeping cancer cells viable. Therapeutic disruption of this riskily balanced homeostasis might change the outcome of many human cancers, particularly those for which no effective therapy is available. Here, we report the use of Fibroblast Growth Factor 2 (FGF2) to demonstrate that further mitogenic activation disrupts cellular homeostasis and strongly sensitizes cancer cells to stress-targeted therapeutic inhibitors. We show that FGF2 enhanced replication and proteotoxic stresses in a K-Ras-driven murine cancer cell model, and combinations of FGF2 and proteasome or DNA damage response-checkpoint inhibitors triggered cell death. CRISPR/Cas9-mediated K-Ras depletion suppressed the malignant phenotype and prevented these synergic toxicities in these murine cells. Moreover, in a panel of human Ewing’s sarcoma family tumor cells, sub-lethal concentrations of bortezomib (proteasome-inhibitor) or VE-821 (ATR-inhibitor) induced cell death when combined with FGF2. Sustained MAPK-ERK1/2 overactivation induced by FGF2 underlies these synthetic lethalities, once late pharmacological inhibition of this pathway restored cell homeostasis and prevented these described synergies. Our results highlight how mitotic signaling pathways frequently overridden in malignant transformation might be exploited to disrupt the risky robustness of cancer cells, ultimately sensitizing them to stress-targeted therapies. This approach provides a new therapeutic rationale for human cancers, with important implications for tumors still lacking effective treatment, and for those that frequently relapse after available therapies.
MetaRiPPquest: A Peptidogenomics Approach for the Discovery of Ribosomally Synthesized and Post-translationally Modified Peptides
Authors: Mohimani Hosein , Gurevich Alexey , Alexander Kelsey L. , Naman C. Benjamin , Leão Tiago , Glukhov Evgenia , Moss Nathan A. , Luzzatto-Knaan Tal , Vargas Fernando , Nothias Louis-Felix , Singh Nitin K. , Sanders Jon G. , Benitez Rodolfo A. S. , Thompson Luke R. , Hamid Md-Nafiz , Morton James T. , Mikheenko Alla , Shlemov Alexander , Korobeynikov Anton , Friedberg Iddo , Knight Rob , Venkateswaran Kasthuri , Gerwick William , Gerwick Lena , Dorrestein Pieter C. , Pevzner Pavel A. 
Published: December 2017

AbstractRibosomally synthesized and post-translationally modified peptides (RiPPs) are an important class of natural products that include many antibiotics and a variety of other bioactive compounds. While recent breakthroughs in RiPP discovery raised the challenge of developing new algorithms for their analysis, peptidogenomic-based identification of RiPPs by combining genome/metagenome mining with analysis of tandem mass spectra remains an open problem. We present here MetaRiPPquest, a software tool for addressing this challenge that is compatible with large-scale screening platforms for natural product discovery. After searching millions of spectra in the Global Natural Products Social (GNPS) molecular networking infrastructure against just six genomic and metagenomic datasets, MetaRiPPquest identified 27 known and discovered 5 novel RiPP natural products.
Does relaxing the infinite sites assumption give better tumor phylogenies? An ILP-based comparative approach
Authors: Bonizzoni Paola , Ciccolella Simone , Della Vedova Gianluca , Soto Mauricio 
Published: December 2017

AbstractMost of the evolutionary history reconstruction approaches are based on the infinite site assumption, which is underlying the Perfect Phylogeny model and whose main consequence is that acquired mutation can never lost. This results in the clonal model used to explain cancer evolution. Some recent results gives a strong evidence that recurrent and back mutations are present in the evolutionary history of tumors [5,21], thus showing that more general models then the Perfect Phylogeny are required. We propose a new approach that incorporates the possibility of losing a previously acquired mutation, extending the Persistent Phylogeny model [1].We exploit our model to provide an ILP formulation of the problem of reconstructing trees on mixed populations, where the input data consists of the fraction of cells in a set of samples that have a certain mutation. This is a fundamental problem in cancer genomics, where the goal is to study the evolutionary history of a tumor. An experimental analysis shows the usefulness of allowing mutation losses, by studying some real and simulated datasets where our ILP approach provides a better interpretation than the one obtained under perfect phylogeny assumption. Finally, we show how to incorporate multiple back mutations and recurrent mutations in our model.
ProteomeVis: a web app for exploration of protein properties from structure to sequence evolution across organisms’ proteomes
Authors: Gilson Amy I. , Durfee Niamh , Razban Rostam M. , Strobelt Hendrick , Dinkla Kasper , Choi Jeong-Mo , Pfister Hanspeter , Shakhnovich Eugene 
Published: December 2017

AbstractMotivationProtein evolution spans time scales and its effects span the length of an organism. A web app named ProteomeVis is developed to provide a comprehensive view of protein evolution in the S.cerevisiaeandE. coliproteomes. ProteomeVis interactively creates protein chain graphs, where edges between nodes represent structure and sequence similarities within user-defined ranges, to study the long time scale effects of protein structure evolution. The short time scale effects of protein sequence evolution is studied by sequence evolutionary rate (ER) correlation analyses with protein properties that span from the molecular to the organismal level.ResultsWe demonstrate the utility and versatility of ProteomeVis by investigating the distribution of edges per node in organismal protein chain universe graphs (oPCUGs) and putative ER determinants. S.cerevisiaeand E.colioPCUGs are scale-free with scaling constants of 1.78 and 1.50, respectively. Both scaling constants can be explained by a previously reported theoretical model describing protein structure evolution (Dokholyanet al.,2002). Protein abundance most strongly correlates with ER among properties in ProteomeVis, with Spearman correlations of −0.51 (p-value<10−10) and −0.46 (p-value<10−10) for S.cerevisiaeandE. coli, respectively. This result is consistent with previous reports that found protein expression to be the most important ER determinant (Zhang and Yang, 2015).AvailabilityProteomeVis is freely accessible athttp://proteomevis.chem.harvard.edu/proteomevis/.Contactshakhnovich@chemistry.harvard.eduSupplementary informationAvailable to download on bioRxiv.
Quantifying and visualising divergence between pairs of phylogenetic trees: implications for phylogenetic reconstruction
Authors: Smith Martin R. 
Published: December 2017

ABSTRACTTree topologies are a primary output of phylogenetic analysis. It is important to understand how such outputs are influenced by the choice of phylogenetic method, and the nature and quality of input data. This often entails the measurement of how closely an output corresponds to an ideal tree topology. The symmetric difference (partition) metric is the only widely-used measure that is defined for trees that contain polytomies, but expresses undesirable behaviour in certain situations.Here I propose a divergence metric for unweighted tree topologies based on quartet statements, which measures the topological information common to two trees. This metric reflects the contributions of both accuracy and precision to tree quality; these components can be decomposed through the use of ternary diagrams. This approach is implemented in a new package for the R statistical environment, and applied to a recent controversy, where it provides a new perspective on the relative merits of Bayesian and parsimony approaches to morphological phylogenetics.
Volatility estimates increase choice switching and relate to prefrontal activity in schizophrenia
Authors: Deserno L. , Boehme R. , Mathys C. , Katthagen T. , Kaminski J. , Stephan K. E. , Heinz A. , Schlagenhauf F. 
Published: December 2017

AbstractBackgroundReward-based decision-making is impaired in patients with schizophrenia (PSZ) as reflected by increased choice switching. The underlying cognitive and motivational processes as well as associated neural signatures remain unknown. Reinforcement Learning (RL) and hierarchical Bayesian learning account for choice switching in different ways. We hypothesized that enhanced choice switching, as seen in PSZ during reward-based decision-making, relates to higher-order beliefs about environmental volatility and examined the associated neural activity.Methods46 medicated PSZ and 43 healthy controls (HC) performed a reward-based decision-making task requiring flexible responses to changing action-outcome contingencies during functional Magnetic Resonance Imaging (fMRI). Detailed computational modeling of choice data was performed, including RL and the hierarchical Gaussian filter (HGF). Trajectories of learning from computational modeling informed the analysis of fMRI data.ResultsA three-level HGF accounted best for the observed choice data. This model revealed a heightened initial belief about environmental volatility and a stronger influence of volatility on lower-level learning of action-outcome contingencies in PSZ as compared to HC. This was replicated in an independent sample of non-medicated PSZ. Beliefs about environmental volatility were reflected by higher activity in dorsolateral prefrontal cortex of PSZ as compared to HC.ConclusionsOur study suggests that PSZ inferred the environment as overly volatile, which may explain increased choice switching. In PSZ, activity in dorsolateral prefrontal cortex was more strongly related to beliefs about environmental volatility. Our computational phenotyping approach may provide useful information to dissect clinical heterogeneity and could improve prediction of outcome.
The physiological regulation of macropinocytosis duringDictyosteliumgrowth and development
Authors: Williams Thomas D. , Kay Robert R. 
Published: December 2017

AbstractMacropinocytosis is a conserved endocytic process used byDictyosteliumamoebae for feeding on liquid medium. To furtherDictyosteliumas a model for macropinocytosis, we developed a high-throughput flow cytometry assay for macropinocytosis, and used it to identify inhibitors and investigate the physiological regulation of macropinocytosis.Dictyosteliumhas two feeding states: phagocytic and macropinocytic. When cells are switched from phagocytic growth on bacteria to liquid media, the rate of macropinocytosis slowly increases, due to increased size and frequency of macropinosomes. Upregulation is triggered by a minimal medium of 3 amino acids plus glucose and likely depends on macropinocytosis itself. Bacteria suppress macropinocytosis while their product, folate, partially suppresses upregulation of macropinocytosis. Starvation, which initiates development, does not of itself suppress macropinocytosis: this can continue in isolated cells, but is shut down by a conditioned-medium factor or activation of PKA signalling. Thus macropinocytosis is a facultative ability ofDictyosteliumcells, regulated by environmental conditions that are identified here.SummaryA high-throughput flow cytometry assay shows that macropinocytosis inD. discoideumis upregulated in the presence of nutrients and absence of bacteria. Development and bacteria induce cells to downregulate macropinocytosis.
Unlocking the biological potential ofEuglena gracilis: evolution, cell biology and significance to parasitism
Authors: Ebenezer ThankGod E. , Zoltner Martin , Burrel Alana , Nenarokova Anna , Vanclová Anna M. G. Novák , Prasad Binod , Soukal Petr , Santana-Molina Carlos , O’Neill Ellis , Nankissoor Nerissa N. , Vadakedath Nithya , Daiker Viktor , Obado Samson , Jackson Andrew P. , Devos Damien , Lukeš Julius , Lebert Michael , Vaughan Sue , Hampl Vladimir , Carrington Mark , Ginger Michael L. , Dacks Joel B. , Kelly Steven , Field Mark C. 
Published: December 2017

AbstractPhotosynthetic euglenids are major components of aquatic ecosystems and relatives of trypanosomes.Euglena gracilishas considerable biotechnological potential and great adaptability, but exploitation remains hampered by the absence of a comprehensive gene catalogue. We address this by genome, RNA and protein sequencing: theE. gracilisgenome is >2Gb, with 36,526 predicted proteins. Large lineage-specific paralog families are present, with evidence for flexibility in environmental monitoring, divergent mechanisms for metabolic control, and novel solutions for adaptation to extreme environments. Contributions from photosynthetic eukaryotes to the nuclear genome, consistent with the shopping bag model are found, together with transitions between kinetoplastid and canonical systems. Control of protein expression is almost exclusively post-transcriptional. These data are a major advance in understanding the nuclear genomes of euglenids and provide a platform for investigating the contributions ofE. gracilisand its relatives to the biosphere.
Cancer subtype identification using somatic mutation data
Authors: Kuijjer Marieke L. , Paulson Joseph N. , Salzman Peter , Ding Wei , Quackenbush John 
Published: December 2017

BACKGROUNDWith the onset of next generation sequencing technologies, we have made great progress in identifying recurrent mutational drivers of cancer. As cancer tissues are now frequently screened for specific sets of mutations, a large amount of samples has become available for analysis. Classification of patients with similar mutation profiles may help identifying subgroups of patients who might benefit from specific types of treatment. However, classification based on somatic mutations is challenging due to the sparseness and heterogeneity of the data.METHODSHere, we describe a new method to de-sparsify somatic mutation data using biological pathways. We applied this method to 23 cancer types from The Cancer Genome Atlas, including samples from 5, 805 primary tumors.RESULTSWe show that, for most cancer types, de-sparsified mutation data associates with phenotypic data. We identify poor prognostic subtypes in three cancer types, which are associated with mutations in signal transduction pathways for which targeted treatment options are available. We identify subtype-drug associations for 14 additional subtypes. Finally, we perform a pan-cancer subtyping analysis and identify nine pan-cancer subtypes, which associate with mutations in four overarching sets of biological pathways.CONCLUSIONSThis study is an important step towards understanding mutational patterns in cancer.
Interpretation of biological experiments changes with evolution of Gene Ontology and its annotations
Authors: Tomczak Aurelie , Mortensen Jonathan M. , Winnenburg Rainer , Liu Charles , Alessi Dominique T. , Swamy Varsha , Vallania Francesco , Lofgren Shane , Haynes Winston , Shah Nigam H. , Musen Mark A. , Khatri Purvesh 
Published: December 2017

ABSTRACTGene Ontology (GO) enrichment analysis is ubiquitously used for interpreting high throughput molecular data and generating hypotheses about underlying biological phenomena of experiments. However, the two building blocks of this analysis — the ontology and the annotations — evolve rapidly. We used gene signatures derived from 104 disease analyses to systematically evaluate how enrichment analysis results were affected by evolution of the GO over a decade. We found low consistency between enrichment analyses results obtained with early and more recent GO versions. Furthermore, there continues to be strong annotation bias in the GO annotations where 58% of the annotations are for 16% of the human genes. Our analysis suggests that GO evolution may have affected the interpretation and possibly reproducibility of experiments over time. Hence, researchers must exercise caution when interpreting GO enrichment analyses and should reexamine previous analyses with the most recent GO version.