bluuebunny/crossref_metadata_2025_split huggingface dataset:
A unique ferredoxin acts as a player in the low-iron response of photosynthetic organisms
Authors: Schorsch Michael , Kramer Manuela , Goss Tatjana , Eisenhut Marion , Robinson Nigel , Osman Deenah , Wilde Annegret , Sadaf Shamaila , Brückler Hendrik , Walder Lorenz , Scheibe Renate , Hase Toshiharu , Hanke Guy T. 
Published: December 2018

SignificanceIron limits the growth of photosynthetic organisms, especially in marine environments. Understanding the response of photosynthetic organisms to changing iron concentrations is therefore important for agriculture and biotechnology. We have identified a protein that is essential for the correct response to changing iron concentrations in photosynthetic bacteria (cyanobacteria). This protein was previously annotated as an electron transfer component of photosynthesis, called Fed2, and contains an iron−sulfur cluster. We tested Fed2, and found that it cannot act in photosynthetic electron transport. The corresponding gene is essential, and is highly conserved between cyanobacteria, algae, and higher plants. By specifically perturbing its function, we could show that it is essential for the low-iron response at the posttranscriptional level.
Inflammation in the hippocampus affects IGF1 receptor signaling and contributes to neurological sequelae in rheumatoid arthritis
Authors: Andersson Karin M. E. , Wasén Caroline , Juzokaite Lina , Leifsdottir Lovisa , Erlandsson Malin C. , Silfverswärd Sofia T. , Stokowska Anna , Pekna Marcela , Pekny Milos , Olmarker Kjell , Heckemann Rolf A. , Kalm Marie , Bokarewa Maria I. 
Published: December 2018

Significance
Aberrant insulin-like growth factor 1 receptor (IGF1R)/insulin receptor signaling in brain has recently been linked to neurodegeneration in diabetes mellitus and in Alzheimer’s disease. In this study, we demonstrate that functional disability and pain in patients with rheumatoid arthritis (RA) and in experimental RA are associated with hippocampal inflammation and inhibition of IGF1R/insulin receptor substrate 1 (IRS1) signal, reproducing an IGF1/insulin-resistant state. This restricts formation of new neurons in the hippocampus, reduces hippocampal volume, and predisposes RA patients to develop neurological symptoms. Improving IRS1 function through down-regulation of IGF1R disinhibits neurogenesis and can potentially ameliorate neurological symptoms. This opens perspectives for drugs that revert IGF1/insulin resistance as an essential complement to the antirheumatic and antiinflammatory arsenal.
Constitutive boost of a K
+
channel via inherent bilayer tension and a unique tension-dependent modality
Authors: Iwamoto Masayuki , Oiki Shigetoshi 
Published: December 2018

Significance
Proteins embedded in the cell membrane are subjected to the membrane’s chemical and physical modifications. Here, we report that cholesterol and other sterols attenuated single-channel activities of a prototypical potassium channel KcsA. Inherent lipid bilayer tension was measured high compared with cell membrane tension, and all tested sterols decreased bilayer tension. Reducing tension by mechanical means also attenuated channel activity. Thus, channel activity was regulated by bilayer tension changes under chemical and physical perturbations. Unlike conventional stretch activation, bilayer tension activated the channel only when the channel was stimulated by intracellular acidic pH. Overall, acidic pH is necessary for activation, but channel opening is fine-tuned by membrane tension in what constitutes a doubly regulated activation modality.
Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria
Authors: Chan Chung Yu , Pedley Anthony M. , Kim Doory , Xia Chenglong , Zhuang Xiaowei , Benkovic Stephen J. 
Published: December 2018

Significance
This study draws on the power of superresolution microscopy to investigate how metabolons behave near different subcellular components. We revealed an interdependent relationship among purinosomes, mitochondria, and microtubules. This further suggests a role for each in maximizing purine production in times of high intracellular demand. With the increasing number of reported metabolons, this study has uncovered a potential general strategy for how metabolons use subcellular networks to facilitate metabolic trade between themselves and other cellular organelles.
A neural data structure for novelty detection
Authors: Dasgupta Sanjoy , Sheehan Timothy C. , Stevens Charles F. , Navlakha Saket 
Published: December 2018

Significance
This work is significant for two reasons. First, considering fly olfaction in the context of a computational algorithm emphasizes features of olfactory processing that might otherwise be less apparent. For example, comparison of prior approaches for novelty detection makes clear that different odors are not just novel vs. familiar, but rather can have various degrees of novelty depending on the similarities between odors. Second, understanding how the fruit fly olfactory circuit detects novel odors can inspire new methods for similar problems in machine learning. In this way, both computer science and neuroscience benefit from the comparison of these two systems.
Noninvasive diagnostic imaging using machine-learning analysis of nanoresolution images of cell surfaces: Detection of bladder cancer
Authors: Sokolov I. , Dokukin M. E. , Kalaparthi V. , Miljkovic M. , Wang A. , Seigne J. D. , Grivas P. , Demidenko E. 
Published: December 2018

Significance
New noninvasive and accurate diagnostic tests of cancer are important. Here we describe such a test, which is applied to the detection of bladder cancer, one of the most common cancers and cause of cancer-related deaths. This method can also be applied for the detection of other cancers, in which cells or body fluid are available for analysis without the need for invasive biopsy, e.g., upper urinary tract, urethra, colorectal and other gastrointestinal, cervical, aerodigestive cancers, etc. Furthermore, the described approach can be extended to detect cell abnormalities beyond cancer as well as to monitor cell reaction to various drugs (nanopharmacology). Thus, this approach may suggest a whole new direction of diagnostic imaging.
Demand for Household Food Waste
Authors: Landry Craig E , Smith Travis A 
Published: December 2018

AbstractWe estimate the demand for food waste within the household using observational data of food stock usage and meal consumption, the net of which forms a proxy for unconsumed food. We find that food waste is a luxury good with an expenditure elasticity ranging from 1.1 to 1.4. The wasting of food is also rather responsive to price: our own‐price elasticity estimates range from ‐1.9 to ‐1.3. We further find differences in the demand for food waste related to household membership structure, human capital, joint preparation of meals within the household, and geographic location.
BIOLITMAP: a web-based geolocated, temporal and thematic visualization of the evolution of bioinformatics publications
Authors: Bazaga Adrián , Valencia Alfonso , JoséRementeria María- 
Published: December 2018

Abstract

Motivation
The fast growth of bioinformatics adds a significant difficulty to assess the contribution, geographical and thematic distribution of the research publications.

Results
To help researchers, grant agencies and general public to assess the progress in bioinformatics, we have developed BIOLITMAP, a web-based geolocation system that allows an easy and sensible exploration of the publications by institution, year and topic.

Availability and implementation
BIOLITMAP is available at http://socialanalytics.bsc.es/biolitmap and the sources have been deposited at https://github.com/inab/BIOLITMAP.

Supplementary information
Supplementary data are available at Bioinformatics online.
ARGDIT: a validation and integration toolkit for Antimicrobial Resistance Gene Databases
Authors: Chiu Jimmy Ka Ho , Ong Rick Twee-Hee 
Published: December 2018

Abstract

Motivation
Antimicrobial resistance is currently one of the main challenges in public health due to the excessive use of antimicrobials in medical treatments and agriculture. The advancements in high-throughput next-generation sequencing and development of bioinformatics tools allow simultaneous detection and identification of antimicrobial resistance genes (ARGs) from clinical, food and environment samples, to monitor the prevalence and track the dissemination of these ARGs. Such analyses are however reliant on a comprehensive database of ARGs with accurate sequence content and annotation. Most of the current ARG databases are therefore manually curated, but this is a time-consuming process and the resulting curation errors could be hard to detect. Several secondary ARG databases consolidate contents from different source ARG databases, and hence modifications in the primary databases might not be propagated and updated promptly in the secondary ARG databases.

Results
To address these problems, a validation and integration toolkit called ARGDIT was developed to validate ARG database fidelity, and merge multiple primary ARG databases into a single consolidated secondary ARG database with optional automated sequence re-annotation. Experimental results demonstrated the effectiveness of this toolkit in identifying errors such as sequence annotation typos in current ARG databases and generating an integrated non-redundant ARG database with structured annotation. A toolkit-oriented workflow is also proposed to minimize the efforts in validating, curating and merging multiple ARG protein or coding sequence databases. Database developers therefore benefit from faster update cycles and lower costs for database maintenance, while ARG pipeline users can easily evaluate the reference ARG database quality.

Availability and implementation
ARGDIT is available at https://github.com/phglab/ARGDIT.

Supplementary information
Supplementary data are available at Bioinformatics online.
Impact of De-escalation on Prognosis of Patients With Bacteremia due to Enterobacteriaceae: A Post Hoc Analysis From a Multicenter Prospective Cohort
Authors: Palacios-Baena Zaira R , Delgado-Valverde Mercedes , Valiente Méndez Adoración , Almirante Benito , Gómez-Zorrilla Silvia , Borrell Núria , Corzo Juan E , Gurguí Mercedes , De la Calle Cristina , García-Álvarez Lara , Ramos Lucía , Gozalo Mónica , Morosini María Isabel , Molina José , Causse Manuel , Pascual Álvaro , Rodríguez-Baño Jesús ,   REIPI/GEIRAS-SEIMC Bacteraemia-MIC Group, de Cueto M , Planes Reig A M , Tubau Quintano F , Peña C , Galán Otalora M E , Ruíz de Alegría C , Cantón R , Lepe J A , Cisneros J M , Torre-Cisneros J , Lara R 
Published: December 2018

Abstract

Background
More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. The aims of this study were to investigate predictors of de-escalation and its impact on the outcome of patients with bloodstream infection due to Enterobacteriaceae (BSI-E).

Methods
A post hoc analysis was performed on a prospective, multicenter cohort of patients with BSI-E initially treated with ertapenem or antipseudomonal β-lactams. Logistic regression was used to analyze factors associated with early de-escalation (EDE) and Cox regression for the impact of EDE and late de-escalation (LDE) on 30-day all-cause mortality. A propensity score (PS) for EDE vs no de-escalation (NDE) was calculated. Failure at end of treatment and length of hospital stay were also analyzed.

Results
Overall, 516 patients were included. EDE was performed in 241 patients (46%), LDE in 95 (18%), and NDE in 180 (35%). Variables independently associated with a lower probability of EDE were multidrug-resistant isolates (odds ratio [OR], 0.50 [95% confidence interval {CI}, .30–.83]) and nosocomial infection empirically treated with imipenem or meropenem (OR, 0.35 [95% CI, .14–.87]). After controlling for confounders, EDE was not associated with increased risk of mortality; hazard ratios (HR) (95% CIs) were as follows: general model, 0.58 (.25–1.31); model with PS, 0.69 (.29–1.65); and PS-based matched pairs, 0.98 (.76–1.26). LDE was not associated with mortality. De-escalation was not associated with clinical failure or length of hospital stay.

Conclusions
De-escalation in patients with monomicrobial bacteremia due to Enterobacteriaceae was not associated with a detrimental impact on clinical outcome.
Identifying the anti-inflammatory response to lipid lowering therapy: a position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology
Authors: Tuñón José , Badimón Lina , Bochaton-Piallat Marie-Luce , Cariou Bertrand , Daemen Mat J , Egido Jesus , Evans Paul C , Hoefer Imo E , Ketelhuth Daniel F J , Lutgens Esther , Matter Christian M , Monaco Claudia , Steffens Sabine , Stroes Erik , Vindis Cécile , Weber Christian , Bäck Magnus 
Published: December 2018

Abstract
Dysregulated lipid metabolism induces an inflammatory and immune response leading to atherosclerosis. Conversely, inflammation may alter lipid metabolism. Recent treatment strategies in secondary prevention of atherosclerosis support beneficial effects of both anti-inflammatory and lipid-lowering therapies beyond current targets. There is a controversy about the possibility that anti-inflammatory effects of lipid-lowering therapy may be either independent or not of a decrease in low-density lipoprotein cholesterol. In this Position Paper, we critically interpret and integrate the results obtained in both experimental and clinical studies on anti-inflammatory actions of lipid-lowering therapy and the mechanisms involved. We highlight that: (i) besides decreasing cholesterol through different mechanisms, most lipid-lowering therapies share anti-inflammatory and immunomodulatory properties, and the anti-inflammatory response to lipid-lowering may be relevant to predict the effect of treatment, (ii) using surrogates for both lipid metabolism and inflammation as biomarkers or vascular inflammation imaging in future studies may contribute to a better understanding of the relative importance of different mechanisms of action, and (iii) comparative studies of further lipid lowering, anti-inflammation and a combination of both are crucial to identify effects that are specific or shared for each treatment strategy.
Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment
Authors: Stiekema Lotte C A , Stroes Erik S G , Verweij Simone L , Kassahun Helina , Chen Lisa , Wasserman Scott M , Sabatine Marc S , Mani Venkatesh , Fayad Zahi A 
Published: December 2018

AbstractAimsSubjects with lipoprotein(a) [Lp(a)] elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-lowering treatment in elevated Lp(a) subjects alters arterial wall inflammation. We evaluated whether evolocumab, which lowers both low-density lipoprotein cholesterol (LDL-C) and Lp(a), attenuates arterial wall inflammation in patients with elevated Lp(a).Methods and resultsIn this multicentre, randomized, double-blind, placebo-controlled study, 129 patients {median [interquartile range (IQR)]: age 60.0 [54.0–67.0] years, Lp(a) 200.0 [155.5–301.5] nmol/L [80.0 (62.5–121.0) mg/dL]; mean [standard deviation (SD)] LDL-C 3.7 [1.0] mmol/L [144.0 (39.7) mg/dL]; National Cholesterol Education Program high risk, 25.6%} were randomized to monthly subcutaneous evolocumab 420 mg or placebo. Compared with placebo, evolocumab reduced LDL-C by 60.7% [95% confidence interval (CI) 65.8–55.5] and Lp(a) by 13.9% (95% CI 19.3–8.5). Among evolocumab-treated patients, the Week 16 mean (SD) LDL-C level was 1.6 (0.7) mmol/L [60.1 (28.1) mg/dL], and the median (IQR) Lp(a) level was 188.0 (140.0–268.0) nmol/L [75.2 (56.0–107.2) mg/dL]. Arterial wall inflammation [most diseased segment target-to-background ratio (MDS TBR)] in the index vessel (left carotid, right carotid, or thoracic aorta) was assessed by 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography. Week 16 index vessel MDS TBR was not significantly altered with evolocumab (−8.3%) vs. placebo (−5.3%) [treatment difference −3.0% (95% CI −7.4% to 1.4%); P = 0.18].ConclusionEvolocumab treatment in patients with median baseline Lp(a) 200.0 nmol/L led to a large reduction in LDL-C and a small reduction in Lp(a), resulting in persistent elevated Lp(a) levels. The latter may have contributed to the unaltered arterial wall inflammation.
Numerical solution of fractional elliptic stochastic PDEs with spatial white noise
Authors: Bolin David , Kirchner Kristin , Kovács Mihály 
Published: December 2018

Abstract
The numerical approximation of solutions to stochastic partial differential equations with additive spatial white noise on bounded domains in $\mathbb{R}^d$ is considered. The differential operator is given by the fractional power $L^\beta $, $\beta \in (0,1)$ of an integer-order elliptic differential operator $L$ and is therefore nonlocal. Its inverse $L^{-\beta }$ is represented by a Bochner integral from the Dunford–Taylor functional calculus. By applying a quadrature formula to this integral representation the inverse fractional-order operator $L^{-\beta }$ is approximated by a weighted sum of nonfractional resolvents $( I + \exp(2 y_\ell) \, L )^{-1}$ at certain quadrature nodes $t_j&gt; 0$. The resolvents are then discretized in space by a standard finite element method. This approach is combined with an approximation of the white noise, which is based only on the mass matrix of the finite element discretization. In this way an efficient numerical algorithm for computing samples of the approximate solution is obtained. For the resulting approximation the strong mean-square error is analyzed and an explicit rate of convergence is derived. Numerical experiments for $L=\kappa ^2-\Delta $, $\kappa&gt; 0$ with homogeneous Dirichlet boundary conditions on the unit cube $(0,1)^d$ in $d=1,2,3$ spatial dimensions for varying $\beta \in (0,1)$ attest to the theoretical results.
SOX2 in cancer stemness: tumor malignancy and therapeutic potentials
Authors: Mamun Mahfuz Al , Mannoor Kaiissar , Cao Jun , Qadri Firdausi , Song Xiaoyuan 
Published: December 2018

AbstractCancer stem cells (CSCs), a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors, posit a significant challenge to develop effective and long-lasting anti-cancer therapies. The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs, thereby leading to CSC-mediated clinical relapse. Accumulating evidence suggests that transcription factor SOX2, a master regulator of embryonic and induced pluripotent stem cells, drives cancer stemness, fuels tumor initiation, and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition, ATP-binding cassette drug transporters, anti-apoptotic and/or pro-survival signaling, lineage plasticity, and evasion of immune surveillance. Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.
Dipeptidyl peptidase-4 inhibitor teneligliptin accelerates recovery from cisplatin-induced acute kidney injury by attenuating inflammation and promoting tubular regeneration
Authors: Iwakura Takamasa , Zhao Zhibo , Marschner Julian A , Devarapu Satish Kumar , Yasuda Hideo , Anders Hans Joachim 
Published: December 2018

AbstractBackgroundCisplatin is an effective chemotherapeutic agent. However, acute kidney injury (AKI) and subsequent kidney function decline limits its use. Dipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to attenuate kidney injury in some in vivo models, but the mechanisms-of-action in tubule recovery upon AKI remain speculative. We hypothesized that DPP-4 inhibitor teneligliptin (TG) can facilitate kidney recovery after cisplatin-induced AKI.MethodsIn in vivo experiment, AKI was induced in rats by injecting 5 mg/kg of cisplatin intravenously. Oral administration of 10 mg/kg of TG, once a day, was started just before injecting cisplatin or from Day 5 after cisplatin injection. In an in vitro experiment, proliferation of isolated murine tubular cells was evaluated with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis and cell counting. Cell viability was analysed by MTT assay or lactate dehydrogenase (LDH) assay.ResultsIn in vivo experiments, we found that TG attenuates cisplatin-induced AKI and accelerates kidney recovery after the injury by promoting the proliferation of surviving epithelial cells of the proximal tubule. TG also suppressed intrarenal tumour necrosis factor-α expression, and induced macrophage polarization towards the anti-inflammatory M2 phenotype, both indirectly endorsing tubule recovery upon cisplatin injury. In in vitro experiments, TG directly accelerated the proliferation of primary tubular epithelial cells. Systematic screening of the DPP-4 substrate chemokines in vitro identified CXC chemokine ligand (CXCL)-12 as a promoted mitogenic factor. CXCL12 not only accelerated proliferation but also inhibited cell death of primary tubular epithelial cells after cisplatin exposure. CXC chemokine receptor (CXCR)-4 antagonism abolished the proliferative effect of TG.ConclusionsThe DPP-4 inhibitor TG can accelerate tubule regeneration and functional recovery from toxic AKI via an anti-inflammatory effect and probably via inhibition of CXCL12 breakdown. Hence, DPP-4 inhibitors may limit cisplatin-induced nephrotoxicity and improve kidney function in cancer patients.
Image-Guided Navigation and Robotics in Spine Surgery
Authors: Kochanski Ryan B , Lombardi Joseph M , Laratta Joseph L , Lehman Ronald A , O’Toole John E 
Published: December 2018

Abstract
Image guidance (IG) and robotics systems are becoming more widespread in their utilization and can be invaluable intraoperative adjuncts during spine surgery. Both are highly reliant upon stereotaxy and either pre- or intraoperative radiographic imaging. While user-operated IG systems have been commercially available longer and subsequently are more widely utilized across centers, robotics systems provide unique theoretical advantages over freehand and IG techniques for placing instrumentation within the spine. While there is a growing plethora of data showing that IG and robotic systems decrease the incidence of malpositioned screws, less is known about their impact on clinical outcomes. Both robotics and IG may be of particular value in cases of substantial deformity or complex anatomy. Indications for the use of these systems continue to expand with an increasing body of literature justifying their use in not only guiding thoracolumbar pedicle screw placement, but also in cases of cervical and pelvic instrumentation as well as spinal tumor resection. Both techniques also offer the potential benefit of reducing occupational exposures to ionizing radiation for the operating room staff, the surgeon, and the patient. As the use of IG and robotics in spine surgery continues to expand, these systems’ value in improving surgical accuracy and clinical outcomes must be weighed against concerns over cost and workflow. As newer systems incorporating both real-time IG and robotics become more utilized, further research is necessary to better elucidate situations where these systems may be particularly beneficial in spine surgery.