bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Food on Bioavailability of Analgesics; Resulting Dosage and Administration Recommendations
Authors: Naraharisetti Suresh Babu , Srour Salma , Xu Yun , Lee David J , Hertz Sharon H , Sahajwalla Chandrahas 
Published: February 2020

Abstract

Objectives
To evaluate currently approved analgesics, that is, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, and serotonin and norepinephrine reuptake inhibitors (SNRIs) used as analgesics, for 1) differences in pharmacokinetic parameters under fed vs fasting conditions and 2) factors involved in dosage recommendations in relation to food.

Design
Systematic review.

Results
Food effect on the rate, extent of absorption, or shape of concentration–time profile can alter the onset of action, duration of action, or tolerability of a medication. Based on 79 analgesic products reviewed, food effect dosage recommendations depend on whether an analgesic will be dosed on a regular interval around-the-clock vs on an as-needed basis, the shape of concentration–time profile, steady-state concentrations, the type of meals used in the pharmacokinetic study, and drug administration with regard to food in clinical trials. Overall, most opioids do not have food restriction and are taken without regard to food, with the exception of OPANA products and XTAMPZA ER. For many NSAIDs, food does not affect absorption characteristics, with the exception of ZORVOLEX and CELEBREX. Although NSAIDs are commonly to be taken without regard to food, prescribers recommend administering them with food to reduce their propensity for gastrointestinal adverse events. A larger percentage of anticonvulsants and SNRIs used as analgesics are taken with food to improve their tolerability. Of all analgesic products, seven NSAIDs and six opioids lack food effect information, maybe due to their approval before Food and Drug Administration food effect guidance.

Conclusions
Overall, because food effects could alter the onset and/or duration of pain relief, analgesic medication should be used as per labeled recommendations for proper pain management.
Germline and somatic mtDNA mutation spectrum of rheumatoid arthritis patients in the Taizhou area, China
Authors: Du Juping , Yu Sufei , Wang Donglian , Chen Shuaishuai , Chen Suyun , Zheng Yufen , Wang Na , Chen Shiyong , Li Jun , Shen Bo 
Published: February 2020

AbstractObjectiveReactive oxygen species are believed to be involved in the onset of RA, and the association between nuclear-encoded mitochondrial respiratory chain-related variants and RA has recently been revealed. However, little is known about the landscape of mitochondrial DNA (mtDNA) variants in RA.MethodsNext-generation sequencing was conducted to profile mtDNA germline and somatic variants in 124 RA patients and 123 age- and sex-matched healthy controls in the Taizhou area, China. Fisher’s exact test, SKAT and SKAT-O were used for gene-burden tests to investigate RA-related variants of mitochondrial genes. Predictive tools were applied to evaluate the pathogenicity of mtDNA variants, and mtDNA haplogroups were assigned according to mtDNA mutations recorded in PhyloTree database. The frequency distribution of mtDNA haplogroups between the groups was compared using χ2 analysis.ResultsWe identified 467 RA-unique and 341 healthy control-unique mtDNA variants, with 443 common variants. Only MT-ATP6 with a significant burden of variants was identified by Fisher’s exact test, SKAT and SKAT-O, even after Bonferroni adjustment, and the enrichment variants in MT-ATP6 was mainly driven by m.8830C&gt;A, m.8833G&gt;C and m.8843T&gt;A variants. Besides, four frequently low-heteroplasmic variants including the three variants above and m.14135T&gt;G of MT-ND5 were detected in RA only; except for m.8830C&gt;A, they are considered potential pathogenicity based on functional predictions. χ2 analysis before Bonferroni adjustment revealed haplogroup F1/F1a to be negatively associated with RA (P &lt; 0.05).ConclusionThese results profiled the landscape of germline and somatic mtDNA variants in RA and supported the effects of mitochondrial genes on RA.
A Low-Cost 3D-Printed Tool with Multiaxial/Angular Vessel Orientation for Microvascular Anastomosis Training
Authors: Alshomer Feras , Alhazmi Bushra , Alowais Fahad , Aldekhayel Salah 
Published: February 2020

Background:
Microsurgical anastomosis is a technically demanding skill. The most difficult part of the learning process was in achieving the necessary orientation and dexterity. In this project, we adopted computer-aided design and desktop 3D-printing in the development of an affordable training model with different levels of vessel orientation and angulation.

Methods:
The training model was designed using CAD software (Rhino3D). The models were then 3D-printed with a thermoplastic polyurethane (TPU 95A) semiflexible filament on a desktop fused deposition modeling, Ultimaker 2 + 3D printer.

Results:
The printed training tool was assembled by fitting the ball-and-socket mechanism between two parts having an overall round table top with integrated vascular clamps. Trial with synthetic and nonliving animal blood vessels shows the utility of the clamps in holding the vessels within the working space. By rotating the top part, a multiaxial vessel orientation from 0 to 360 degrees was achieved. The top part was also capable of multiangular orientation of the vessels (±30 degrees) regardless of its axial orientation during vessel anastomosis. For the 3D-printing process, the average printing time was about 3.5 hours with a cost of 1.3$ per material.

Conclusions:
The utility of desktop 3D printing represents an affordable modality in microsurgical training. The designed model is capable of providing a trainee with multiaxial and multiangular vessel orientation during the anastomosis process. To our knowledge, the adoption of this technology in the field of microsurgery training has never been investigated before.
Intraocular lens far peripheral vision: image detail and negative dysphotopsia
Authors: Simpson Michael J. 
Published: February 2020

Purpose:
To evaluate negative dysphotopsia in the far periphery of the pseudophakic eye by generating simulated images of text charts.

Setting:
Consultancy.

Design:
Laboratory study.

Methods:
Simulated images of a peripheral text chart were created using a ray-trace model of a pseudophakic eye. The point spread function varies strongly with a radial location. Retinal angles subtended at the second nodal point were used to linearly scale retinal locations to a polar plot in object space, weighting rays by the object luminance, the total transmittance, and a cosine normalization for pupil effects. Improved scaling using a phakic 70-year-old eye was also explored.

Results:
Images demonstrate a distinct shadow with a 2.5 mm pupil between the upper limit of the text image formed by the intraocular lens (IOL) and a second larger image due to light missing the IOL. The shadow is rapidly softened by a small increase in pupil diameter.

Conclusions:
The images verified characteristics that previously were only inferred indirectly: (1) With a 2.5 mm pupil, there is a prominent dark shadow. (2) Light missing the IOL experiences lower power and forms a larger image and also comes from a lower visual angle. (3) A small increase in pupil diameter causes the shadow to fade. The calculations showed that imaging in the far periphery is very different for the pseudophakic eye in comparison with the phakic eye. The limit of the focused image is probably the primary cause of the shadow, yet relatively few patients find this to be bothersome.
Multiple Progressive Thermopreconditioning Improves Cardiac Ischemia/Reperfusion-induced Left Ventricular Contractile Dysfunction and Structural Abnormality in Rat
Authors: Chen Yueh-Hsi , Chiang Chih-Yao , Chang Tzu-Ching , Chien Chiang-Ting 
Published: February 2020

Background.
Triple progressive thermopreconditioning (3PTP) may induce high Hsp-70 expression to maintain cardiac function. We suggest that 3PTP may reduce myocardial ischemia/reperfusion (I/R) injury during organ transplantation through Bag3/Hsp-70 mediated defense mechanisms.

Methods.
Male Wistar rats were divided into sham control group and 72 h after 3PTP in a 42°C water bath (3PTP) group. Rats underwent 60 min of ischemia by occlusion of the left anterior descending coronary artery followed by 240 min reperfusion. Hemodynamic parameters, including the electrocardiogram, microcirculation, heart rate, left ventricular end-diastolic pressure, maximal rate of rise (+dp/dt), and fall (−dp/dt) in the left ventricular pressure for index of contraction and relaxation were determined. Myocardial infarct size was evaluated by the Evans blue-2,3,5-triphenyltetrazolium chloride method. 3PTP-induced protective mechanisms were determined by Western blot and immunohistochemistry.

Results.
Cardiac I/R depressed cardiac microcirculation, induced S-T segment elevation, and R-R and P-R interval elongation increased infarct size associated with erythrocyte extravasation, leukocytes and macrophage/monocyte infiltration, granulocyte colony-stimulating factor, poly(ADP-ribose) polymerase 1 stain, and transferase-mediated dUTP-biotin nick end labeling positive cells. However, 3PTP evoked significant cardioprotection against I/R injury, characterized by the increased +dp/dt value and the decreased elevated left ventricular end-diastolic pressure, erythrocyte extravasation, leukocyte and macrophage/monocyte infiltration, granulocyte colony-stimulating factor expression, poly(ADP-ribose) polymerase 1 expression, transferase-mediated dUTP-biotin nick end labeling positive cells, and fragmentation and infarct area. In addition, 3PTP increased Hsp-70 and Bag3 expression and decreased Bax/Bcl-2 ratio, but did not affect the Beclin-1 and LC3-II/LC3-I ratio in the heart with I/R injury.

Conclusions.
3PTP therapies may through Bag3 upregulation alleviate I/R injury-induced left ventricular structural deterioration and dysfunction.
Spatial inequality hides the burden of dog bites and the risk of dog-mediated human rabies
Authors: Puente-León Micaela De la , Levy Michael Z. , Toledo Amparo M. , Recuenco Sergio , Shinnick Julianna , Castillo-Neyra Ricardo 
Published: February 2020

ABSTRACTCurrently, there is an active rabies outbreak in the dog population of Arequipa, Peru. Inhabitants of the city are bitten by both pets and free-roaming dogs; therefore, the risk of human rabies transmission is concerning. Our objective was to estimate the rate of dog bites in the city and to identify factors associated with going or not going to a medical facility for rabies follow-up. To this end, we conducted a door-to-door survey of 4,000 houses in 21 urban and 21 peri-urban communities. We then analyzed associations between attaining follow-up rabies care and various socioeconomic factors, stratifying by urban and peri-urban localities. We found that the rate of dog bites in peri-urban communities (12.4%) was approximately three times higher than urban areas (4.0%). Among the people who were bitten, a significantly greater number of people in urban areas got follow-up rabies care than those in peri-urban areas.
Genomic signals found using RNA sequencing support conservation of walleye (Sander vitreus) in a large freshwater ecosystem
Authors: Thorstensen Matt J. , Jeffrey Jennifer D. , Treberg Jason R. , Watkinson Douglas A. , Enders Eva C. , Jeffries Ken M. 
Published: February 2020

AbstractRNA sequencing is an effective approach for studying an aquatic species with little prior molecular information available, yielding both physiological and genomic data, but its genetic applications are not well-characterized. We investigate this possible role for RNA sequencing for population genomics in Lake Winnipeg, Manitoba, Canada, walleye (Sander vitreus). Lake Winnipeg walleye represent the largest component of the second-largest freshwater fishery in Canada. In the present study, large female walleye were sampled via nonlethal gill biopsy over two years at three spawning sites representing a latitudinal gradient in the lake. Genetic variation from sequenced messenger RNA was analyzed for neutral and adaptive markers to investigate population structure and possible adaptive variation. We find low population divergence (FST= 0.0095), possible northward gene flow, and outlier loci that vary latitudinally in transcripts associated with cell membrane proteins and cytoskeletal function. These results indicate that Lake Winnipeg walleye may be effectively managed as a single demographically connected metapopulation with contributing subpopulations, and suggest genomic differences possibly underlying observed phenotypic differences. Because RNA sequencing data can yield physiological in addition to genetic information discussed here, we argue that it is useful for addressing diverse molecular questions in the conservation of freshwater species.
Ubiquitination and Phosphorylation are Independently Required for Epsin-Mediated Internalization of Cargo inS. cerevisiae
Authors: Sen Arpita , Hsieh Wen-Chieh , Hanna Claudia B. , Hsu Chuan-Chih , Pearson McKeith , Tao W. Andy , Aguilar R. Claudio 
Published: February 2020

ABSTRACTIt is well-known that in addition to its classical role in protein turnover, ubiquitination is required for a variety of membrane protein sorting events. However, and despite substantial progress in the field, a long-standing question remains:given that all ubiquitin (Ub) units are identical, how do different elements of the sorting machinery recognize their specific cargoes?Here we provide an answer to this question as we discovered a mechanism based on the coincidence detection of lysine ubiquitination and Ser/Thr phosphorylation for the endocytic adaptor epsin to mediate the internalization of the yeast Na+pump Ena1.Internalization of Ena1-GFP was abolished in double epsin knock-out inS. cerevisiaeand was rescued by re-introducing either one of the 2 yeast epsins, Ent1 or Ent2 in an UIM (Ub InteractingMotif)-dependent manner. Further, our results indicate that ubiquitination of its C-terminal Lys1090is needed for internalization of Ena1 and requires the arrestin-related-trafficking adaptor, Art3.We determined that in addition to ubiquitination of K1090, the presence of a Ser/Thr-rich patch (S1076TST1079) within Ena1 was also essential for its internalization. Our results suggest that this ST motif is targeted for phosphorylation by casein kinases. Nevertheless, phosphorylation of this S/T patch was not required for ubiquitination. Instead, ubiquitination of K1090and phosphorylation of the ST motif were independently needed for epsin-mediated internalization of Ena1.We propose a model in which a dual detection mechanism is used by Ub-binding elements of the sorting machinery to differentiate among multiple Ub-cargoes.
Inferring Models with Alternative Stable States from Independent Observations
Authors: Tekwa Edward W. , Krkošek Martin , Pinsky Malin L. 
Published: February 2020

AbstractMultiple attractors and alternative stable states are defining features of scientific theories in ecology and evolution, implying that abrupt regime shifts can occur and that outcomes can be hard to reverse. Here we describe a statistical inferential framework that uses independent, noisy observations with low temporal resolution to support or refute multiple attractor process models. The key is using initial conditions to choose among a finite number of expected outcomes using a nonstandard finite mixture methodology. We apply the framework to contemporary issues in social-ecological systems, coral ecosystems, and chaotic systems, showing that incorporating history allows us to statistically infer process models with alternative stable states while minimizing false positives. Further, in the presence of disturbances and oscillations, alternative stable states can help rather than hamper inference. The ability to infer models with alternative stable states across natural systems can help accelerate scientific discoveries, change how we manage ecosystems and societies, and place modern theories on firmer empirical ground.
A fast genetically encoded fluorescent sensor for faithfulin vivoacetylcholine detection in mice, fish, worms and flies
Authors: Borden Philip M. , Zhang Peng , Shivange Amol V. , Marvin Jonathan S. , Cichon Joseph , Dan Chuntao , Podgorski Kaspar , Figueiredo Antonio , Novak Ondrej , Tanimoto Masashi , Shigetomi Eiji , Lobas Mark A. , Kim Hyuntae , Zhu Paula K. , Zhang Yajun , Zheng W. Sharon , Fan ChengCheng , Wang Guangfu , Xiang Bowen , Gan Li , Zhang Guang-Xian , Guo Kaiming , Lin Li , Cai Yuan , Yee Andrew G. , Aggarwal Abhi , Ford Christopher P. , Rees Douglas C. , Dietrich Dirk , Khakh Baljit S. , Dittman Jeremy S. , Gan Wen-Biao , Koyama Minoru , Jayaraman Vivek , Cheer Joseph F. , Lester Henry A. , Zhu J. Julius , Looger Loren L. 
Published: February 2020

AbstractHere we design and optimize a genetically encoded fluorescent indicator, iAChSnFR, for the ubiquitous neurotransmitter acetylcholine, based on a bacterial periplasmic binding protein. iAChSnFR shows large fluorescence changes, rapid rise and decay kinetics, and insensitivity to most cholinergic drugs. iAChSnFR revealed large transients in a variety of slice andin vivopreparations in mouse, fish, fly and worm. iAChSnFR will be useful for the study of acetylcholine in all animals.
Modeling and analysis of site-specific mutations in cancer identifies known plus putative novel hotspots and bias due to contextual sequences
Authors: Trevino Victor 
Published: February 2020

AbstractIn cancer, recurrently mutated sites in DNA and proteins, calledhotspots, are thought to be raised by positive selection and therefore important due to its potential functional impact. Although recent evidence for APOBEC enzymatic activity have shown that specific types of sequences are likely to be false, the identification of putative hotspots is important to confirm either its functional role or its mechanistic bias. In this work, an algorithm and a statistical model is presented to detect hotspots. The model consists of abeta-binomialcomponent plus fixed effects that efficiently fits the distribution of mutated sites. The algorithm employs an optimal step-wise approach to find the model parameters. Simulations show that the proposed algorithmic model is highly accurate for common hotspots. The approach has been applied to TCGA mutational data from 33 cancer types. The results show that well-known cancer hotspots are easily detected. Besides, novel hotspots are also detected. An analysis of the sequence context of detected hotspots show a preference for TCG sites that may be related to APOBEC or other unknown mechanistic biases. The detected hotspots are available online inhttp://bioinformatica.mty.itesm.mx/HotSpotsAnnotations.
Metagenomics workflow for hybrid assembly, differential coverage binning, transcriptomics and pathway analysis (MUFFIN)
Authors: Van Damme Renaud , Hölzer Martin , Viehweger Adrian , Müller Bettina , Bongcam-Rudloff Erik , Brandt Christian 
Published: February 2020

AbstractMetagenomics has redefined many areas of microbiology. However, metagenome-assembled genomes (MAGs) are often fragmented, primarily when sequencing was performed with short reads. Recent long-read sequencing technologies promise to improve genome reconstruction. However, the integration of two different sequencing modalities makes downstream analyses complex. We, therefore, developed MUFFIN, a complete metagenomic workflow that uses short and long reads to produce high-quality bins and their annotations. The workflow is written by using Nextflow, a workflow orchestration software, to achieve high reproducibility and fast and straightforward use. This workflow also produces the taxonomic classification and KEGG pathways of the bins and can be further used by providing RNA-Seq data (optionally) for quantification and annotation. We tested the workflow using twenty biogas reactor samples and assessed the capacity of MUFFIN to process and output relevant files needed to analyze the microbial community and their function. MUFFIN produces functional pathway predictions and if providedde novotranscript annotations across the metagenomic sample and for each bin.Author SummaryRVD did the development and design of MUFFIN and wrote the first draft; BM and EBR did the critical reading and correction of the manuscript; MH did the critical reading of the manuscript and the general adjustments for the metagenomic workflow; AV did the critical reading of the manuscript and adjustments for the taxonomic classifications. CB supervised the project, did the workflow design, helped with the implementation, and revised the manuscript.
Post-copulatory sexual selection is associated with sperm aggregate quality inPeromyscusmice
Authors: Hook Kristin A. , Weber W. David , Fisher Heidi S. 
Published: February 2020

AbstractIn some species, sperm form coordinated groups that are hypothesized to improve their swimming performance in competitive contexts or to navigate through the viscous fluids of the female reproductive tract. Here we investigate sperm aggregation across closely-related species ofPeromyscusmice that naturally vary by mating system to test the predictions that sperm aggregates (1) are faster than solitary sperm in species that females mate multiply to aid cells in sperm competition, and (2) outperform solitary sperm cells in viscous environments. We find significant variation in the size of sperm aggregates, which negatively associates with relative testis mass, a proxy for sperm competition risk, suggesting that post-copulatory sexual selection has a stabilizing effect on sperm group size. Moreover, our results show that sperm aggregates are faster than solitary sperm in some, but not all, species, and this can vary by fluid viscosity. Of the two species that produce the largest and most frequent groups, we find that sperm aggregates from the promiscuousP. maniculatusare faster than solitary sperm in every experimentally viscous environment but aggregation provides no such kinematic advantage under these same conditions for the monogamousP. polionotus. The reduced performance ofP. polionotusaggregates is associated with less efficient aggregate geometry and the inclusion of immotile or morphological abnormal sperm. Our cross-species comparison yields insight into the evolution of sperm social behaviors, provides evidence of extensive variation in thePeromyscuslineage, and reveals that differences in sperm aggregate quality associate with post-copulatory sexual selection.