bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure–safety–efficacy analysis of single-agent ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3 maintenance study
Authors: Gupta Neeraj , Labotka Richard , Liu Guohui , Hui Ai-Min , Venkatakrishnan Karthik 
Published: April 2016

SummaryBackground Ixazomib is the first oral, small molecule proteasome inhibitor to reach phase 3 trials. The current analysis characterized the exposure-safety and exposure-efficacy relationships of ixazomib in patients with relapsed/refractory multiple myeloma (MM) with a purpose of recommending an approach to ixazomib dosing for maintenance therapy. Methods Logistic regression was used to investigate relationships between ixazomib plasma exposure (area under the curve/day; derived from individual apparent clearance values from a published population pharmacokinetic analysis) and safety/efficacy outcomes (hematologic [grade ≥ 3 vs ≤ 2] or non-hematologic [grade ≥ 2 vs ≤ 1] adverse events [AEs], and clinical benefit [≥stable disease vs progressive disease]) using phase 1 data in relapsed/refractory MM (NCT00963820; N = 44). Results Significant relationships to ixazomib exposure were observed for five AEs (neutropenia, thrombocytopenia, rash, fatigue, and diarrhea) and clinical benefit (p < 0.05). Dose–response relationships indicated a favorable benefit/risk ratio at 3 mg and 4 mg weekly, which are below the maximum tolerated dose of 5.5 mg. At 3 mg, the model predicted that: 37 % of patients will achieve clinical benefit; incidence of grade ≥ 3 neutropenia and thrombocytopenia will be 10 % and 23 %, respectively; and incidence of grade ≥ 2 rash, fatigue, and diarrhea will be 8 %, 19 %, and 19 %, respectively. Conclusions Based on the findings, patients in the phase 3 maintenance trial will initiate ixazomib at a once-weekly dose of 3 mg, increasing to 4 mg if acceptable tolerability after 4 cycles, to provide maximum clinical benefit balanced with adequate tolerability.
Partial or non-union after triple arthrodesis in children: Does it really matter?
Authors: Wicks Eric D. , Morscher Melanie A. , Newton Meadow , Steiner Richard P. , Weiner Dennis S. 
Published: April 2016

Purpose Triple arthrodesis is a commonly performed salvage procedure to correct hindfoot deformity. Non-union is considered an undesirable radiographic outcome; however, the clinical ramifications of this are not as well defined. The purpose of this study was to determine the incidence of partial or complete radiographic non-union after triple arthrodesis in children and characterize the clinical consequences. Methods An IRB-approved retrospective review of triple arthrodesis surgeries in patients less than 16 years of age performed by a single surgeon (DSW) identified 159 cases meeting the inclusion criteria. Plain radiographs were reviewed for bony fusion (defined as over 80 % radiographic bony union of the subtalar, calcaneocuboid, and talonavicular bones) and charts for clinical outcomes (pain, return to activity, and subsequent hindfoot surgeries). Statistics were used to compare the fused and unfused cases, with p < 0.05 considered to be significant. Results Of the 159 cases included in the study, 9 % did not achieve at least 80 % plain film radiographic union. The fused and unfused groups had similar clinical outcomes. Only one patient required surgery for sequelae of symptoms arising from a pseudoarthrosis related to the triple arthrodesis. The fused and unfused groups were similar in terms of gender and pin removal time, but differed significantly in surgical age and underlying diagnosis. Conclusions This is one of the largest case series of pediatric triple arthrodesis surgery presented in the literature. This study demonstrated that good clinical outcomes can be achieved despite the lack of radiographic union after triple arthrodesis surgery in children. Level of evidence IV.
Teacher autonomy support reduces adolescent anxiety and depression: An 18‐month longitudinal study
Authors: Yu Chengfu , Li Xian , Wang Shujun , Zhang Wei 
Published: April 2016

ABSTRACTGrounded in stage–environment fit theory, this study adopts a longitudinal design to examine the contribution of autonomy support from teachers to reducing adolescent anxiety and depression. A total of 236 Chinese adolescents (57.38% females, Mage = 14.34) completed questionnaires on teacher autonomy support, basic psychological needs satisfaction, school engagement, anxiety, and depression in the fall and spring semesters of their 7th and 8th grade years. The results showed that teacher autonomy support in the fall of 7th grade boosted basic psychological needs satisfaction in the spring of 7th grade; this, in turn, increased school engagement in the fall of 8th grade, which subsequently decreased anxiety and depression in the spring of 8th grade. These findings demonstrated the significant effect of teacher autonomy support on reducing adolescent anxiety and depression; furthermore, it highlighted the mediating roles of basic psychological needs satisfaction and school engagement in this relationship.
Epochs in the depressor/pressor balance of the renin–angiotensin system
Authors: Colafella Katrina M. Mirabito , Hilliard Lucinda M. , Denton Kate M. 
Published: April 2016

The renin–angiotensin system (RAS) plays a commanding role in the regulation of extracellular fluid homoeostasis. Tigerstadt and Bergman first identified the RAS more than two centuries ago. By the 1980s a voyage of research and discovery into the mechanisms and actions of this system led to the development of drugs that block the RAS, which have become the mainstay for the treatment of cardiovascular and renal disease. In the last 25 years new components of the RAS have come to light, including the angiotensin type 2 receptor (AT2R) and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1–7) [Ang(1–7)]/Mas receptor (MasR) axis. These have been shown to counter the classical actions of angiotensin II (AngII) at the predominant angiotensin type 1 receptor (AT1R). Our studies, and those of others, have demonstrated that targeting these depressor RAS pathways may be therapeutically beneficial. It is apparent that the evolution of both the pressor and depressor RAS pathways is distinct throughout life and that the depressor/pressor balance of the RAS vary between the sexes. These temporal patterns of expression suggest that therapies targeting the RAS could be optimized for discrete epochs in life.
Axial superresolution via multiangle TIRF microscopy with sequential imaging and photobleaching
Authors: Fu Yan , Winter Peter W. , Rojas Raul , Wang Victor , McAuliffe Matthew , Patterson George H. 
Published: April 2016

Significance
Superresolution microscopy has made significant progress with molecule localization, stimulated emission depletion, and structured illumination techniques. Here we describe a simple method to achieve ∼20-nm axial resolution based on total internal reflection fluorescence (TIRF) microscopy. In this approach, serial fluorescent images at multiple depths within the normal ∼200-nm TIRF illumination zone are obtained by the serial imaging and photobleaching at multiple TIRF excitation angles. These images with ∼20-nm axial depth intervals are then simply stacked together to differentiate the relative distributions of multiple proteins in the axial direction. Moreover, images collected during the photobleaching step of the experiment can be analyzed using Bayesian analysis of fluorophore blinking and bleaching to generate superresolution images in the lateral direction for each depth.
Unraveling the dynamics and structure of functionalized self-assembled monolayers on gold using 2D IR spectroscopy and MD simulations
Authors: Yan Chang , Yuan Rongfeng , Pfalzgraff William C. , Nishida Jun , Wang Lu , Markland Thomas E. , Fayer Michael D. 
Published: April 2016

SignificanceSelf-assembled monolayers (SAMs) are a form of nanotechnology that enables the functionalization of surfaces with single layers of chemically designed structures having tuned properties. In contrast to the characterization of time-average static structures, it is challenging to measure the dynamic behavior of SAMs on the timescales of molecular motions, i.e. picoseconds. Here we combine 2D IR spectroscopy and molecular dynamics (MD) simulations to investigate alkyl chain monolayers functionalized with a head group. The dynamics reported by the head group are induced by the alkyl chain motions. For example, it was determined that SAMs with higher alkyl chain gauche defect content have faster dynamics caused by more frequent chain conformational fluctuations.
Drug-induced adverse events prediction with the LINCS L1000 data
Authors: Wang Zichen , Clark Neil R. , Ma’ayan Avi 
Published: April 2016

Abstract
Motivation: Adverse drug reactions (ADRs) are a central consideration during drug development. Here we present a machine learning classifier to prioritize ADRs for approved drugs and pre-clinical small-molecule compounds by combining chemical structure (CS) and gene expression (GE) features. The GE data is from the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs. Using various benchmarking methods, we show that the integration of GE data with the CS of the drugs can significantly improve the predictability of ADRs. Moreover, transforming GE features to enrichment vectors of biological terms further improves the predictive capability of the classifiers. The most predictive biological-term features can assist in understanding the drug mechanisms of action. Finally, we applied the classifier to all  &gt;20 000 small-molecules profiled, and developed a web portal for browsing and searching predictive small-molecule/ADR connections.
Availability and Implementation: The interface for the adverse event predictions for the  &gt;20 000 LINCS compounds is available at http://maayanlab.net/SEP-L1000/.
Contact: avi.maayan@mssm.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
GenomeRunner web server: regulatory similarity and differences define the functional impact of SNP sets
Authors: Dozmorov Mikhail G. , Cara Lukas R. , Giles Cory B. , Wren Jonathan D. 
Published: April 2016

Abstract
Motivation: The growing amount of regulatory data from the ENCODE, Roadmap Epigenomics and other consortia provides a wealth of opportunities to investigate the functional impact of single nucleotide polymorphisms (SNPs). Yet, given the large number of regulatory datasets, researchers are posed with a challenge of how to efficiently utilize them to interpret the functional impact of SNP sets.
Results: We developed the GenomeRunner web server to automate systematic statistical analysis of SNP sets within a regulatory context. Besides defining the functional impact of SNP sets, GenomeRunner implements novel regulatory similarity/differential analyses, and cell type-specific regulatory enrichment analysis. Validated against literature- and disease ontology-based approaches, analysis of 39 disease/trait-associated SNP sets demonstrated that the functional impact of SNP sets corresponds to known disease relationships. We identified a group of autoimmune diseases with SNPs distinctly enriched in the enhancers of T helper cell subpopulations, and demonstrated relevant cell type-specificity of the functional impact of other SNP sets. In summary, we show how systematic analysis of genomic data within a regulatory context can help interpreting the functional impact of SNP sets.
Availability and Implementation: GenomeRunner web server is freely available at http://www.integrativegenomics.org/.
Contact: mikhail.dozmorov@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Lung inflammation stalls Th17-cell migration en route to the central nervous system during the development of experimental autoimmune encephalomyelitis
Authors: Kanayama Masashi , Danzaki Keiko , He You-Wen , Shinohara Mari L. 
Published: April 2016

Abstract
Recruiting pathogenic T cells to the central nervous system (CNS) is a critical step during the development of experimental autoimmune encephalomyelitis (EAE). Here, we report that the absence of autophagy and microtubule-associated protein 1A/1B-light chain 3-associated phagocytosis significantly delayed the onset of EAE in Atg7 conditional knockout (Atg7 CKO) mice in myeloid cells. T-helper cell-cell priming appeared to be normal in the Atg7 CKO mice, but the mice showed significant accumulation of Th17 cells in the lung. The data suggested that the stalling of Th17 cells in the lung en route to the CNS caused the delay. The lung of Atg7 CKO mice, in which we previously demonstrated spontaneous mild inflammation, showed high expression of CCL20, a chemokine that attracts Th17 cells. We have also shown that LPS intranasal instillation delayed EAE onset, suggesting that pulmonary inflammation has an impact on EAE development. Based on our data, therapeutic immunomodulation targeted to the lung, rather than systemically, might be a possible future option to treat multiple sclerosis.
Choice-induced biases in perception
Authors: Luu Long , Stocker Alan A 
Published: April 2016

AbstractIllusions provide a great opportunity to study how perception is affected by both the observer's expectations and the way sensory information is represented1,2,3,4,5,6. Recently, Jazayeri and Movshon7reported a new and interesting perceptual illusion, demonstrating that the perceived motion direction of a dynamic random dot stimulus is systematically biased when preceded by a motion discrimination judgment. The authors hypothesized that these biases emerge because the brain predominantly relies on those neurons that are most informative for solving the discrimination task8, but then is using the same neural weighting profile for generating the percept. In other words, they argue that these biases are “mistakes” of the brain, resulting from using inappropriate neural read-out weights. While we were able to replicate the illusion for a different visual stimulus (orientation), our new psychophysical data suggest that the above interpretation is likely incorrect: Biases are not caused by a read-out profile optimized for solving the discrimination task but rather by the specific choices subjects make in the discrimination task on any given trial. We formulate this idea as a conditioned Bayesian observer model and show that it can explain the new as well as the original psychophysical data. In this framework, the biases are not caused by mistake but rather by the brain's attempt to remain ‘self-consistent’ in its inference process. Our model establishes a direct connection between the current perceptual illusion and the well-known phenomena of cognitive consistency and dissonance9,10.
Trans‐Amazonian natal homing in giant catfish
Authors: Duponchelle Fabrice , Pouilly Marc , Pécheyran Christophe , Hauser Marilia , Renno Jean‐François , Panfili Jacques , Darnaude Audrey M. , García‐Vasquez Aurea , Carvajal‐Vallejos Fernando , García‐Dávila Carmen , Doria Carolina , Bérail Sylvain , Donard Ariane , Sondag Francis , Santos Roberto V. , Nuñez Jesus , Point David , Labonne Maylis , Baras Etienne 
Published: April 2016

Summary

Knowledge of fish migration is a prerequisite to sustainable fisheries management and preservation, especially in large international river basins. In particular, understanding whether a migratory lifestyle is compulsory or facultative, and whether adults home to their natal geographic area is paramount to fully appraise disruptions of longitudinal connectivity resulting from damming.

In the Amazon, the large migratory catfishes of the Brachyplatystoma genus are apex predators of considerable interest for fisheries. They are believed to use the entire length of the basin to perform their life cycle, with hypothesized homing behaviours. Here, we tested these hypotheses, using the emblematic B. rousseauxii as a model species.

We sampled adults close to major breeding areas in the Amazon basin (upper Madeira and upper Amazonas) and assessed their lifetime movements by measuring variations in 87Sr/86Sr along transverse sections of their otoliths (ear stones) using laser ablation multicollector mass spectrometry (LA‐MC‐ICPMS).

We demonstrate that larvae migrate downstream from the Andean piedmont to the lower Amazon, where they grow over a protracted period before migrating upstream as adults. Contrary to prevailing inferences, not all fish spend their nursery stages in the Amazon estuary. By contrast, the passage in the lower or central Amazon seems an obligate part of the life cycle. We further evidence that most adults home to their natal geographic area within the Madeira sub‐basin. Such long‐distance natal homing is exceptional in purely freshwater fishes.

Synthesis and applications. By using otolith microchemistry, we were able to demonstrate a seemingly compulsory basin‐wide migratory life cycle of large Amazonian catfishes. This makes them the organisms performing the longest migrations (>8000 km) in fresh waters. This exceptional life history is already jeopardized by two dams recently built in the Madeira River, which block a major migration route and access to a substantial part of their spawning grounds. Major impacts can be anticipated from the current and forthcoming hydroelectric development in the Amazon basin, not only on the populations and fisheries of this apex predator, but also on Amazonian food webs through trophic cascades.
Evolutionary responses of invasive grass species to variation in precipitation and soil nitrogen
Authors: Nguyen Monica A. , Ortega Amy E. , Nguyen Kurt Q. , Kimball Sarah , Goulden Michael L. , Funk Jennifer L. 
Published: April 2016

SummaryGlobal climate models suggest that many ecosystems will experience reduced precipitation over the next century and the consequences for invasive plant performance are largely unknown. Annual invasive species may be able to quickly evolve traits associated with drought escape or tolerance through rapid genetic changes.We investigated the influence of 5 years of water and nitrogen manipulations on trait values in a southern California grassland system. Seeds from two annual grass species (Avena barbataandBromus madritensis) were collected from experimental plots and grown in a common environment over two generations. We measured 14 physiological, morphological, phenological and reproductive traits.Both species displayed phenotypic differences depending on the water treatment from which they were collected, but not depending on the nitrogen treatment. Both species displayed trait values characteristic of drought escape (e.g. earlier flowering inA. barbataandB. madritensis, lower water‐use efficiency inB. madritensis) when grown from the seeds collected from plots that experienced five years of reduced precipitation. Furthermore,A. barbataindividuals grown from the seeds collected from drought plots had higher reproductive output and higher photosynthetic performance than individuals grown from water addition plots, with individuals grown from ambient plots displaying intermediate trait values. Notably, we found no phenotypic variation among treatments for six root traits.Synthesis. Trait differences were observed following two generations in a common garden, suggesting that treatment differences were genetically based. This suggests that populations were responding to selection over the 5 years of water manipulations, a remarkably short time period. The rapid evolutionary responses observed here may help these two widespread invasive grass species thrive under reduced precipitation scenarios, which could have important implications for fire dynamics, invasive species management and native plant restoration in communities invaded by annual grasses.
Normalising desistance: contextualising marijuana and cocaine use careers in young adults
Authors: Roussell Aaron , Omori Marisa 
Published: April 2016

AbstractAlthough there is a vast literature on drug use and addiction, there is little work that addresses the long‐term use of drugs within the general population. We take a more contextual look in examining longitudinal drug use patterns over the course of 14 years for a representative sample of young adults in their late teens and early twenties in the United States using the National Longitudinal Survey of Youth (NLSY). We use a growth trajectory modelling approach for cocaine and marijuana users to determine general use careers. Using contextual and life‐course variables, we then estimate a multinomial logistic regression model to predict group membership. In addition to establishing general use career groups, we ask how well mainstream theories comport with our findings and how the different chemical makeup of cocaine and marijuana influence our findings. We find four general use career groups: (i) high use/late desistance; (ii) peaked use/strong desistance; (iii) low use; and (iv) stable use/gradual desistance. Our results suggest similar careers for users of both drugs, with desistance over time as the rule for all groups. We also find some support for life‐course and contextual factors in drug using patterns, but our findings challenge other psychological and criminological theories.
Interaction of Government Tiers and Central Banks in a Federation: An Empirical Test
Authors: Claeys Peter , Ramos Raul , Suriñach Jordi 
Published: April 2016

AbstractFiscal rules are necessary to protect monetary policy from the consequences of unsustainable or active fiscal policy for inflation. Monetary unions, such as the Economic and Monetary Union (EMU), require even stronger fiscal rules to avoid free riding by regional fiscal authorities on the common monetary policy. By contrast, in a fiscal federation, the federal government internalises the effect of active regional policies on the overall price level. Federal fiscal policy contributes to price stability either by enforcing fiscal rules or by adjusting its own stance. Following Canzoneri, Cumby and Diba (2001), we test whether federal and regional governments in Germany behave in an active or passive way. We find evidence of a spillover effect of unsustainable policies on other regions. The German federal government offsets the effect on the price level by running passive policies. The Bundesbank's prime objective of price stability is therefore endorsed by fiscal policy. The results have implications for the regulation of fiscal policies in the EMU.
Investigation of Ballistic Evidence through an Automatic Image Analysis and Identification System
Authors: Kara Ilker 
Published: April 2016

AbstractAutomated firearms identification (AFI) systems contribute to shedding light on criminal events by comparison between different pieces of evidence on cartridge cases and bullets and by matching similar ones that were fired from the same firearm. Ballistic evidence can be rapidly analyzed and classified by means of an automatic image analysis and identification system. In addition, it can be used to narrow the range of possible matching evidence. In this study conducted on the cartridges ejected from the examined pistol, three imaging areas, namely the firing pin impression, capsule traces, and the intersection of these traces, were compared automatically using the image analysis and identification system through the correlation ranking method to determine the numeric values that indicate the significance of the similarities. These numerical features that signify the similarities and differences between pistol makes and models can be used in groupings to make a distinction between makes and models of pistols.