bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shelf Life and Efficacy of Diagnostic Eye Drops
Authors: Hanssens Jean-Marie , Quintana-Giraldo Carolina , Jacques Sandrine , El-Zoghbi Nohade , Lampasona Vanessa , Langevin Camille , Bouchard Jean-François 
Published: October 2018

SIGNIFICANCE
Pharmaceutical companies recommend discarding ophthalmic drugs 28 days after opening. This study shows that diagnostic eye drops have a low risk of contamination over a 7-month period in a controlled clinical setup. The diagnostic efficiency seems to be preserved over this period.

PURPOSE
The aim of this study was to evaluate the preservation period and the efficacy of ophthalmic preparations, such as 0.5% proparacaine hydrochloride, 1% tropicamide, 2.5% phenylephrine hydrochloride, and 1% cyclopentolate hydrochloride ophthalmic solution in a clinical and controlled setting.

METHODS
Thirty-eight primary eye care students were recruited to participate in the study. They used 25 bottles of each diagnostic drop at the Clinique Universitaire de la Vision for a 7-month period. An analysis of the bacterial contamination was repeated 10 times using both an agar plate and a nutrient broth at 0, 2, 4, 6, and 8 weeks and at 3, 4, 5, 6, and 7 months. The anesthetic, mydriatic, and cycloplegic effects were tested after 7 months of use and compared with nonopened ophthalmic bottles.

RESULTS
During the 7-month period, 4971 drops of proparacaine, 3219 drops of tropicamide and phenylephrine, and 1896 drops of cyclopentolate were administered to the patients. A total of 226 contacts between bottles and biological tissues were reported. After the 10 inoculation sessions on the agar medium at the predetermined times, no bacterial and fungal contamination was noted. No patient reported eye infections for 2 weeks after the drop instillation. Moreover, there was no difference in the efficacy when compared with new drops.

CONCLUSIONS
According to the results of the current study, diagnostic eye drops can be used with a low contamination risk beyond the recommendation date of 28 days up to 7 months, with the same efficacy, in a controlled clinical context.
iPhone-based Pupillometry: A Novel Approach for Assessing the Pupillary Light Reflex
Authors: McAnany J. Jason , Smith Brandon M. , Garland Amy , Kagen Steven L. 
Published: October 2018

SIGNIFICANCE
The response of the pupil to a flash of light, the pupillary light reflex (PLR), is an important measure in optometry and in other fields of medicine that is typically evaluated by qualitative observation. Here we describe a simple, portable, iPhone-based pupillometer that quantifies the PLR in real time.

PURPOSES
The purposes of this study were to describe a novel application that records the PLR and to compare its technical capabilities with a laboratory-based infrared (IR) camera system.

METHODS
Pupil sizes were measured from 15 visually normal subjects (age, 19 to 65 years) using an IR camera system and the Sensitometer test. This test elicits pupillary constriction using the iPhone flash, records pupil size using the camera, and provides measurements in real time. Simultaneous recordings were obtained with the Sensitometer test and IR camera, and two measures were calculated: (1) dark-adapted steady-state pupil size and (2) minimum pupil size after the flash. The PLR was defined as the difference between these two measures. Pupil size was also recorded during the redilation phase after the flash. Bland-Altman analysis was used to assess the limits of agreement between the two methods.

RESULTS
Statistically significant correlations between the IR and Sensitometer test measures were found for the PLR (r = 0.91, P < .001) and redilation size (r = 0.65, P = .03). Bland-Altman analysis indicated a mean PLR difference of 6% between these two methods. The PLR limit of agreement was 14%, indicating that 95% of subjects are expected to have IR and Sensitometer test measurements that differ by 14% or less. Bland-Altman analysis indicated a mean redilation size difference of 1% between the two methods; the limit of agreement was 5%.

CONCLUSIONS
There is excellent agreement between pupil responses recorded using the Sensitometer test and IR camera. The Sensitometer test provides a highly promising approach for simple, portable, inexpensive pupillary measurements.
The Effect of Traditional Chinese Medicine Zhike-Houpu Herbal Pair on Depressive Behaviors and Hippocampal Serotonin 1A Receptors in Rats After Chronic Unpredictable Mild Stress
Authors: Xia Zian , Zhang Chunhu , Du Yuanhao , Huang Wei , Xing Zhihua , Cao Hui , Nie Kechao , Wang Yang , Xiong Xingui , Yang Bo 
Published: October 2018

ABSTRACTObjectiveZhike-Houpu herbal pair (ZKHPHP) is a well-known Chinese medicine to treat gastrointestinal motility dysfunction. Recently, many researchers have found that some of the compounds of ZKHPHP such as meranzin hydrate and magnolol have antidepressant effects. However, little is known about the antidepressant mechanism of ZKHPHP. Therefore, the main aim of the study is to evaluate the antidepressant-like effects of ZKHPHP and its possible mechanism of action on 5-hydroxytryptamine receptor 1A (HTR1A) in the hippocampus CA1 region in rats exposed to chronic unpredictable mild stress.MethodsMale Sprague Dawley rats were randomly divided into the following six groups: normal, model, ZKHPHP (3 g/kg), ZKHPHP (10 g/kg), ZKHPHP (20 g/kg), and ZKHPHP (30 g/kg);n= 8 per group. We exposed the rats to chronic unpredictable mild stress and then assessed antidepressant-like effects of ZKHPHP by measuring weight change, observing the open-field test, and measuring sucrose water consumption. The antidepressant mechanism was examined by measuring the effect of ZKHPHP on HTR1A protein expression and HTR1A mRNA expression in the hippocampus CA1 region by using immunohistochemistry analysis, Western blotting, and real-time reverse transcription-polymerase chain reaction.ResultsZKHPHP (10 or 20 g/kg) reduced the incidence of depressive-like behaviors and increased HTR1A protein and HTR1A mRNA expression in the hippocampus CA1 in rats displaying depressive behavior, whereas ZKHPHP (3 or 30 g/kg) had no obvious effect on the measured depression indicators.ConclusionsThese data show that ZKHPHP has antidepressant-like effects based on a chronic unpredictable mild stress-induced depression model in rats. ZKHPHP may be attractive as an antidepressant because of its beneficial effects on depression and the absence of gastrointestinal dysregulation, which is a frequently observed unintended effect of many commonly used antidepressive medications.
Antithrombotic Stewardship: Assessing Use of Computerized Clinical Decision Support Tools to Enhance Safe Prescribing of Direct Oral Anticoagulants in Hospitalized Patients
Authors: Ahuja Tania , Raco Veronica , Papadopoulos John , Green David 
Published: October 2018

Abstract
Prescribing patterns for oral anticoagulants in patients with nonvalvular atrial fibrillation and venous thromboembolism is shifting from vitamin K antagonists, such as warfarin to the direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, and apixaban. Although many hospital systems have implemented clinical decision support or enhanced monitoring for patients prescribed warfarin, there is limited evidence to suggest similar levels of enhanced monitoring for DOACs. The antithrombotic stewardship team at our institution developed guidelines and implemented computerized clinical decision support (CCDS) tools to enhance medication and patient safety related to the DOACs. We sought to assess the safety and effectiveness of these CCDS tools available to clinicians upon DOAC prescription in hospitalized patients. We performed a retrospective review of 121 patients who received at least two doses of a DOAC from January 2013 to July 2014. We assessed dosing of the DOAC according to the CCDS provided upon order entry. Adherence to CCDS was 80% (n = 24), 75% (n = 46), and 87% (n = 27) in the dabigatran, apixaban, and rivaroxaban group, respectively. Our data demonstrate that implementing CCDS for DOACs into the electronic medical record may ensure safe prescribing of high-risk medications.
Social and Behavioral Consequences of Participation in HIV Preventive Vaccine Trials in the ANRS COHVAC Cohort
Authors: Durier Christine , Desaint Corinne , Launay Odile 
Published: October 2018

Abstract:
From 1992 to 2007, the ANRS (France Recherche Nord & Sud Sida-HIV Hépatites) set up a network of healthy volunteers at low risk of HIV infection and participating in preventive HIV vaccine phase I and II trials. The objectives of the ANRS COHVAC volunteer cohort include the social consequences of trial participation and their sexual behavior over time. For 488 volunteers who received a vaccine candidate, 462 selection files were collected, and from 2008 to 2016, 355 volunteers participated in the prospective cohort, including self-administered and face-to-face questionnaires administered annually. The volunteer population is relatively old, with social characteristics and engagement in society rather high. Most volunteers and people around them well accepted the trials, and participation in vaccine trials was not followed by increased risk-taking regarding HIV infection years later.
Exceptional Risk: Healthy Volunteers' Perceptions of HIV/AIDS Clinical Trials
Authors: Cottingham Marci D. , Kalbaugh Julianne M. , Swezey Teresa , Fisher Jill A. 
Published: October 2018

Abstract:
As with all early-stage testing of investigational drugs, clinical trials targeting HIV/AIDS can pose unknown risks to research subjects. Unlike sick participants seeking a therapeutic benefit, the motivations and barriers for healthy volunteers are more complex and understudied. Drawing on interviews and clinical trial data from 178 healthy volunteers, we examine how they perceive HIV/AIDS studies in the early stages of testing. A subset of healthy volunteers see phase I HIV/AIDS studies as particularly risky for reasons ranging from fear of catching the disease or having long-lasting and uncomfortable side effects to inexplicable fears that they cannot even articulate. Some participants have had past negative experiences in such trials that inform these views, but others cite information from staff and other participants as influential. Healthy volunteers' general fears concerning AIDS also shape their views of participating in phase I HIV/AIDS clinical trials.
Superiority of Multidetector Computed Tomography With 3-Dimensional Volume Rendering Over Plain Radiography in the Assessment of Spinal Surgical Instrumentation Complications in Patients With Cancer
Authors: Debnam James M. , Chi Tzehping L. , Ketonen Leena , Wei Wei , Guha-Thakurta Nandita 
Published: October 2018

Objective
The objective of this study was to compare multidetector computed tomography (MDCT) images with volume-rendered translucent display (VRTLD) series to plain radiographs for evaluating spinal surgical instrumentation after resection and reconstruction for spinal malignancies.

Methods
In 44 patients with tumor resection and spinal reconstruction, 17 with complications, 3 neuroradiologists evaluated plain radiographs, MDCT images alone, VRTLD images alone, and MDCT images with VRTLD images for identifying complications in 3 categories: subsidence/migration, construct fracture, and screw loosening. Each category was scored as 1 (complications), 2 (no complications), or 3 (not sure), and the minimum score was used for analyses. Clinical/surgical outcomes were the reference standard.

Results
Sensitivity, specificity, and accuracy (95% confidence interval), respectively, were as follows: MDCT/VRTLD, 100%, 100%, 100% (91.96%–100.00%); MDCT alone, 88.24%, 100%, 95.45% (84.53%–99.44%); VRTLD alone, 82.35%, 96.3%, 90.91% (78.33%–97.47%); plain radiographs, 52.94%, 100%, 81.82% (67.29%–91.81%).

Conclusions
Multidetector computed tomography with VRTLD series seems best for evaluation of spinal instrumentation after tumor resection and reconstruction.
Effect of Statistically Iterative Image Reconstruction on Vertebral Bone Strength Prediction Using Bone Mineral Density and Finite Element Modeling: A Preliminary Study
Authors: Anitha D. , Subburaj Karupppasamy , Kopp Felix K. , Mei Kai , Foehr Peter , Burgkart Rainer , Sollmann Nico , Maegerlein Christian , Kirschke Jan S. , Noel Peter B. , Baum Thomas 
Published: October 2018

Abstract
Statistical iterative reconstruction (SIR) using multidetector computed tomography (MDCT) is a promising alternative to standard filtered back projection (FBP), because of lower noise generation while maintaining image quality. Hence, we investigated the feasibility of SIR in predicting MDCT-based bone mineral density (BMD) and vertebral bone strength from finite element (FE) analysis. The BMD and FE-predicted bone strength derived from MDCT images reconstructed using standard FBP (FFBP) and SIR with (FSIR) and without regularization (FSIRB0) were validated against experimental failure loads (Fexp). Statistical iterative reconstruction produced the best quality images with regard to noise, signal-to-noise ratio, and contrast-to-noise ratio. Fexp significantly correlated with FFBP, FSIR, and FSIRB0. FFBP had a significant correlation with FSIRB0 and FSIR. The BMD derived from FBP, SIRB0, and SIR were significantly correlated. Effects of regularization should be further investigated with FE and BMD analysis to allow for an optimal iterative reconstruction algorithm to be implemented in an in vivo scenario.
Autophagy Induction Ameliorates Inflammatory Responses in Intestinal Ischemia–Reperfusion Through Inhibiting NLRP3 Inflammasome Activation
Authors: Wang Zishuo , Li Zhenlu , Feng Dongcheng , Zu Guo , Li Yang , Zhao Yan , Wang Guangzhi , Ning Shili , Zhu Jie , Zhang Feng , Yao Jihong , Tian Xiaofeng 
Published: October 2018

ABSTRACT
Intestinal ischemia/reperfusion (I/R)-induced systemic inflammation leads to multiple organ dysfunction syndrome. Previous studies have indicated that the NOD-like receptor protein (NLRP)3 inflammasome modulates intestinal inflammation; however, the pathophysiological mechanisms remain unclear. Autophagy is a critical metabolic mechanism that promotes cellular survival following ischemic injury. Recently, basal autophagy has been implicated in the alleviation of extensive inflammation. However, the role of autophagy in NLRP3 inflammasome activation in intestinal I/R-induced inflammatory injury remains undefined. In the present study, we examined whether NLRP3 inflammasome activation is induced in mice subjected to intestinal I/R injury, which is measured as increased apoptosis-associated speck-like protein containing a CARD levels, caspase-1 activity, and interleukin-1β (IL-1β) secretion. Importantly, the in-vitro results showed that NLRP3 knockdown decreases proinflammatory cytokine production and increases resistance to hypoxia/reoxygenation (H/R)-triggered inflammation. Subsequently, we demonstrated a critical role for autophagy in suppressing intestinal I/R-induced NLRP3 inflammasome activation in vivo. Furthermore, we showed that the loss of autophagy activates inflammasome-mediated IL-1β secretion, which aggravates H/R injury, and NLRP3 knockdown reverses these effects. Collectively, these results directly implicated the homeostatic process of autophagy and NLRP3 inflammasome in ischemic bowel disease and identified a novel pathway for therapeutic intervention in intestinal I/R.
Sepsis Increases Muscle Proteolysis in Severely Burned Adults, but Does not Impact Whole-Body Lipid or Carbohydrate Kinetics
Authors: Murton Andrew , Bohanon Fredrick J. , Ogunbileje John O. , Capek Karel D. , Tran Ellen A. , Chao Tony , Sidossis Labros S. , Porter Craig , Herndon David N. 
Published: October 2018

ABSTRACT
Sepsis is a common and often fatal consequence of severe burn injury, but its exact effects on whole body and muscle metabolism in the burn patient is unclear. To address this, 13 septic and 11 nonseptic patients (age: 36.9 ± 13.0 years) with burns encompassing >30% of their total body surface area underwent muscle protein kinetic studies under postabsorptive conditions using bolus injections of ring-13C6 and 15N phenylalanine isotopes. In parallel, whole-body lipid and carbohydrate kinetics were assessed using constant infusions of [U-13C6]palmitate, [6,6-2H2]glucose, and [2H5]glycerol, and during a 2-h hyperinsulinemic euglycemic clamp. Muscle mRNA levels of genes implicated in the development of muscle cachexia were assessed by qPCR. Fractional breakdown rates of mixed-muscle proteins were found to be 2.4-fold greater in septic versus nonseptic patients (P < 0.05). No discernable differences in fractional synthetic rate of mixed-muscle proteins or rate of appearance of plasma free fatty acids, glycerol, or glucose could be observed between patient groups, although the latter was significantly associated with burn size (P < 0.05). Hyperinsulinemia stimulated whole-body glucose uptake and suppressed endogenous glucose production and whole-body lipolytic rate to equivalent degrees in both groups. Muscle mRNA levels of genes spanning autophagy, lysosomal, and ubiquitin proteasome-mediated proteolysis were not enhanced in septic versus nonseptic patients. Our results demonstrate that accelerated muscle proteolysis appears to be the principal metabolic consequence of sepsis in severe burn patients and could be a contributing factor to the accelerated loss of muscle mass in these individuals. The exact mechanistic basis for these changes remains unclear.
Multi-objective formulation of MSA for phylogeny estimation
Authors: Nayeem Muhammad Ali , Bayzid Md. Shamsuzzoha , Rahman Atif Hasan , Shahriyar Rifat , Rahman M. Sohel 
Published: October 2018

AbstractMultiple sequence alignment (MSA) is a basic step in many analyses in computational biology, including predicting the structure and function of proteins, orthology prediction and estimating phylogenies. The objective of MSA is to infer the homology among the sequences of chosen species. Commonly, the MSAs are inferred by optimizing a single function or objective. The alignments estimated under one criterion may be different to the alignments generated by other criteria, inferring discordant homologies and thus leading to different evolutionary histories relating the sequences. In recent past, researchers have advocated for the multi-objective formulation of MSA, to address this issue, where multiple conflicting objective functions are being optimized simultaneously to generate a set of alignments. However, no theoretical or empirical justification with respect to a real-life application has been shown for a particular multi-objective formulation. In this study, we investigate the impact of multi-objective formulation in the context of phylogenetic tree estimation. Employing multi-objective metaheuristics, we demonstrate that trees estimated on the alignments generated by multi-objective formulation are substantially better than the trees estimated by the state-of-the-art MSA tools, including PASTA, MUSCLE, CLUSTAL, MAFFT etc. We also demonstrate that highly accurate alignments with respect to popular measures like sum-of-pair (SP) score and total-column (TC) score do not necessarily lead to highly accurate phylogenetic trees. Thus in essence we ask the question whether a phylogeny-aware metric can guide us in choosing appropriate multi-objective formulations that can result in better phylogeny estimation. And we answer the question affirmatively through carefully designed extensive empirical study. As a by-product we also suggest a methodology for primary selection of a set of objective functions for a multi-objective formulation based on the association with the resulting phylogenetic tree.
Hox genes mediate the escalation of sexually antagonistic traits in water striders
Authors: Johan Crumière Antonin Jean , Khila Abderrahman 
Published: October 2018

AbstractSexual conflict occurs when traits favoured in one sex impose fitness costs on the other sex. In the case of sexual conflict over mating rate, the sexes often undergo antagonistic coevolution and escalation of traits that enhance female’s resistance to mating and traits that increase male’s persistence. How this escalation in sexually antagonistic traits is established during ontogeny remains unclear. In the water striderRhagovelia antilleana, male persistence traits consist of sex combs in the forelegs and multiple rows of spines and a thick femur in the rearlegs. Female resistance trait consists of a prominent spike-like projection of the pronotum. RNAi knockdown against the Hox geneSex Combs Reducedresulted in the reduction of both the sex comb in males and the pronotum projection in females. RNAi against the Hox geneUltrabithoraxresulted in the complete loss or reduction of all persistence traits in male rearlegs. These results demonstrate that Hox genes can mediate sex-specific escalation of antagonistic traits along the body axis of both sexes.
rCASC: reproducible Classification Analysis of Single Cell sequencing data
Authors: Alessandrì Luca , Beccuti Marco , Arigoni Maddalena , Olivero Martina , Romano Greta , De Libero Gennaro , Pace Luigia , Cordero Francesca , Calogero Raffaele A 
Published: October 2018

AbstractSummarySingle-cell RNA sequencing has emerged as an essential tool to investigate cellular heterogeneity, and highlighting cell sub-population specific signatures. Nowadays, dedicated and user-friendly bioinformatics workflows are required to exploit the deconvolution of single-cells transcriptome. Furthermore, there is a growing need of bioinformatics workflows granting both functional, i.e. saving information about data and analysis parameters, and computation reproducibility, i.e. storing the real image of the computation environment. Here, we present rCASC a modular RNAseq analysis workflow allowing data analysis from counts generation to cell sub-population signatures identification, granting both functional and computation reproducibility.Availability and ImplementationrCASC is part of the reproducible bioinfomatics project. rCASC is a docker based application controlled by a R package available at https://github.com/kendomaniac/rCASC.Supplementary informationSupplementary data are available at rCASC github
Variant pathogenic prediction models VSRFM and VSRFM-s, the importance of splicing and allele frequency
Authors: Cabrera-Alarcon JL , Garcia-Martinez J 
Published: October 2018

ABSTRACTCurrently, there are available several tools to predict the effect of variants, with the aim of classify variants in neutral or pathogenic. In this study, we propose a new model trained over ensemble scores with two particularities, first we consider minor frequency allele from gnomAD and second, we split variants based on their splicing for training each specific model. Variants Stacked Random Forest Model (VSRFM) was constructed for variants not involved in splicing and Variants Stacked Random Forest Model for splicing (VSRFM-s) was trained for variants affected by splicing. Comparing these scores with their constituent scores used as features, our models showed the best outcomes. These results were confirmed using an independent data set from Clinvar database, with similar results.