bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Diurnal and Day of Week Online Search Patterns Related to Common Eye Conditions
Authors: Deiner Michael S. , McLeod Stephen D. , Schallhorn Julie M. , Chodosh James , Hwang Daniel H. , Lietman Thomas M. , Porco Travis C. 
Published: July 2020

AbstractImportanceStudies suggest diurnal patterns of some eye conditions. Leveraging new information sources such as online search data to learn more about such patterns could improve understanding of patient eye-related conditions and well-being and improve timing of clinical and remote eye care.ObjectiveTo investigate our hypothesis that the public is likely to consistently search about different eye conditions at different hours of the day or days of week, we conducted an observational study using search data for terms related to eye conditions such as conjunctivitis. We asked if search volumes reflected diurnal or day-of-week patterns and if those patterns were distinct from each other.DesignHourly search data for eye-related and control search terms for 2018 were analyzed and compared.SettingData from 10 USA states.ExposureInternet search.ParticipantsPopulations that searched Google’s search engine using our chosen study terms.Main Outcome MeasuresCyclical hourly and weekly online search patterns.ResultsDistinct diurnal (p<0.001 for all search terms) and day-of-week search patterns for eye-related terms were observed but with differing peak time periods and cyclic strengths. Some diurnal patterns represented reported clinical patterns. Of the eye related terms, “conjunctivitis” and “pink eye” had the strongest diurnal cyclic patterns based on peak-to-trough ratios. Stronger signal was restricted to and peaked in mornings, and amplitude was higher on weekdays. In contrast, “dry eyes” had a higher amplitude diurnal pattern on weekends, with stronger signal occurring over a broader evening to morning period and peaking in early morning.Conclusions and RelevanceThe frequency of online searches for various eye conditions can show cyclic patterns according to time of day or week. Further studies to understand the reasons for these variations may help supplement current clinical understanding of eye symptom presentation and improve the timeliness of patient messaging and care interventions.Key PointsQuestionDo online public search engine queries for different eye-health terms follow hourly or daily patterns and do the patterns differ from each other or reflect what is known clinically?FindingsUnique hourly and day of week eye health related search patterns appear diurnal and can reflect what has been observed clinically.MeaningOnline search data may reflect timing of eye conditions and could improve clinical understanding of eye-related symptom occurrence, including outside of clinics. Knowing precisely when patient’s eye condition interests increase holds promise -for example to optimize timing and availability of local or remote eye care resources.
Probabilistic divergence of a TBM methodology from the ideal protocol
Authors: Runthala Ashish 
Published: July 2020

AbstractProtein structural information is essential for the detailed mapping of a functional protein network. For a higher modelling accuracy and quicker implementation, template based algorithms have been extensively deployed and redefined. The methods only assess the predicted structure against its native state/template, and do not estimate the accuracy for each modelling step. A divergence measure is postulated to estimate the modelling accuracy against its theoretical optimal benchmark. By freezing the domain boundaries, the divergence measures are predicted for the most crucial steps of a modelling algorithm. To precisely refine the score using weighting constants, big data analysis could further be deployed.
Self-incompatibility limits sexual reproduction rather than environmental conditions in an invasive aquatic plant
Authors: Portillo Lemus Luis O. , Bozec Michel , Harang Marilyne , Coudreuse Julie , Haury Jacques , Stoeckel Solenn , Barloy Dominique 
Published: July 2020

SummaryFruitfulness and fertility are important components of sexual reproductive success in plants, and often depends on environmental conditions and reproductive systems. For invasive plants, fruitfulness and fertility control their ecological success and adaptation in invaded ecosystems. We studied which factors bring about fruitfulness and fertility in invasive populations of the aquatic plantLudwigia grandiflorasubsp.hexapetala.We analysed fruitfulness and fertility of 37 populations growing under variable climatic conditions in Western Europe, and sub-sampled fruitful and fruitless populations grown in common controlled conditions. We carried out self- and cross-pollinations and measured their floral biometrics.Environmental conditions, and temperature in particular, did not affect fruitfulness and fertility in-situ or in common controlled environments. Hand-pollinations resulted in fruit production by individuals sampled from fruitless populations when pollen came from fruitful populations, and by individuals sampled from fruitful populations whatever the origin of pollen. Floral biometrics evidenced the existence of two floral morphs that overlapped with fruitfulness, and individual incompatibility.Our results rebutted the hypothesis that environmental conditions control fruitfulness and fertility in these invasive populations. We instead found that fruit and seed production were controlled by a reproductive system involving a self-incompatible approach herkogamous morph and a self-compatible reverse herkogamous morph. We assessed the floral morphs distribution worldwide of fruitless and fruitful native and invasive populations that matched our results at larger scale. Our results may constitute the first evidence of a possible heteromorphic self-incompatible system inLudwigiapopulations and in Onagraceae phylogeny. It calls for further investigations on reproductive systems in this plant family. Finally, the observation that the self-incompatible morph seemed to be the world most invasive morph in this species tackles our understanding of biological and ecological conditions for invasiveness.Synthesis. Our study showed that fruitfulness and fertility in the aquatic invasive plant,Ludwigia grandiflorasubsp.hexapetaladepend on a self-incompatibility system coinciding with two floral morphs, rather than environmental conditions and limitations. These new explanations on the sexual success ofLudwigiainvasive populations will help defining new predictions about its worldwide spreads and ecological success, and will help reappraising future management plans.
VIRIDIC – a novel tool to calculate the intergenomic similarities of prokaryote-infecting viruses
Authors: Moraru Cristina , Varsani Arvind , Kropinski Andrew M. 
Published: July 2020

AbstractNucleotide based intergenomic similarities are useful to understand how viruses are related with each other and to classify them. Here we have developed VIRIDIC, which implements the traditional algorithm used by the International Committee on Taxonomy of Viruses (ICTV), Bacterial and Archaeal Viruses Subcommittee, to calculate virus intergenomic similarities. When compared with other software, VIRIDIC gave the best agreement with the traditional algorithm. Furthermore, it proved best at estimating the relatedness between more distantly related phages, relatedness that other tools can significantly overestimate. In addition to the intergenomic similarities, VIRIDIC also calculates three indicators of the alignment ability to capture the relatedness between viruses: the aligned fractions for each genome in a pair and the length ratio between the two genomes. The main output of VIRIDIC is a heatmap integrating the intergenomic similarity values with information regarding the genome lengths and the aligned genome fraction. VIRIDIC is available at viridic.icbm.de, both as a web-service and a stand-alone tool. It allows fast analysis of large phage genome datasets, especially in the stand-alone version, which can be run on the user’s own servers and can be integrated in bioinformatics pipelines. VIRIDIC was developed having viruses ofBacteriaandArchaeain mind, however, it could potentially be used for eukaryotic viruses as well, as long as they are monopartite.
QUALIS: The journal ranking system undermining the impact of Brazilian science
Authors: Jaffé Rodolfo 
Published: July 2020

AbstractA system called QUALIS was implemented in Brazil in 2009, intended to rank graduate programs from different subject areas and promote selected national journals. Since this system uses a complicated suit of criteria (differing among subject areas) to group journals into discrete categories, it could potentially create incentives to publish in low-impact journals ranked highly by QUALIS. Here I assess the influence of the QUALIS journal ranking system on the global impact of Brazilian science. Brazil shows a steeper decrease in the number of citations per document since the implementation of this QUALIS system, compared to the top Latin American countries publishing more scientific articles. All subject areas showed some degree of bias, with social sciences being usually more biased than natural sciences. Lastly, the decrease in the number of citations over time proved steeper in a more biased subject area, suggesting a faster shift towards low-impact journals. Overall, the findings documented here suggest that the QUALIS system has undermined the global impact of Brazilian science, and reinforce a recent recommendation from an official committee evaluating graduate programs to eliminate QUALIS. A system based on impact metrics could avoid introducing distorted incentives, and thereby boost the global impact of Brazilian science.
CHO/LY-B cell growth under limiting sphingolipid supply: correlation between lipid composition and biophysical properties of sphingolipid-restricted cell membranes+
Authors: Monasterio Bingen G. , Jiménez-Rojo Noemi , García-Arribas Aritz B. , Riezman Howard , Goñi Félix M. , Alonso Alicia 
Published: July 2020

ABSTRACTSphingolipids (SL) are ubiquitous in mammalian cell membranes, yet there is little data on the behavior of cells under SL-restriction conditions. LY-B cells derive from a CHO line in which serine palmitoyl transferase (SPT), thusde novoSL synthesis, is suppressed, while maintaining the capacity of taking up and metabolizing exogenous sphingoid bases from the culture medium. In the present study LY-B cells were adapted to grow in a fetal bovine serum (FBS)-deficient medium to avoid external uptake of lipids. The lowest FBS concentration that allowed LY-B cell growth, though at a slow rate, under our conditions was 0.04%, i.e. 250-fold less than the standard (10%) concentration. Cells grown under limiting SL concentrations remained viable for at least 72 h. Enriching with sphingomyelin the SL-deficient medium allowed the recovery of control LY-B cell growth rates. Studies including whole cells, plasma membrane preparations, and derived lipid vesicles were carried out. Laurdan fluorescence was recorded to measure membrane molecular order, showing a significant decrease in the rigidity of LY-B cells, not only in plasma membrane but also in whole cell lipid extract, as a result of SL limitation in the growth medium. Plasma membrane preparations and whole cell lipid extracts were also studied using atomic force microscopy in the force spectroscopy mode. Force measurements demonstrated that lower breakthrough forces were required to penetrate samples obtained from SL-poor LY-B cells than those obtained from control cells. Mass-spectroscopic analysis was also a helpful tool to understand the rearrangement undergone by the LY-B cell lipid metabolism. The most abundant SL in LY-B cells, sphingomyelin, decreased by about 85% as a result of SL limitation in the medium, the bioactive lipid ceramide and the ganglioside precursor hexosylceramide decreased similarly, together with cholesterol. Quantitative SL analysis showed that a 250-fold reduction in sphingolipid supply to LY-B cells led to a 6-fold decrease in membrane sphingolipids, underlining the resistance to changes in composition of these cells. Plasma membrane compositions exhibited similar changes, at least qualitatively, as the whole cells with SL restriction. A linear correlation was observed between the sphingomyelin concentration in the membranes, the degree of lipid order as measured by laurdan fluorescence, and membrane breakthrough forces assessed by atomic force microscopy. Concomitant changes were detected in glycerophospholipids under SL-restriction conditions.
The Torsin/ NEP1R1-CTDNEP1/ Lipin axis regulates nuclear envelope lipid metabolism for nuclear pore complex insertion
Authors: Jacquemyn Julie , Foroozandeh Joyce , Vints Katlijn , Swerts Jef , Verstreken Patrik , Gounko Natalia V. , Gallego Sandra F. , Goodchild Rose 
Published: July 2020

AbstractTorsin ATPases of the endoplasmic reticulum (ER) and nuclear envelope (NE) lumen inhibit Lipin-mediated phosphatidate (PA) to diacylglycerol (DAG) conversion by an unknown mechanism. This excess PA metabolism is implicated inTOR1A/TorsinA diseases, but it is unclear whether it explains why Torsin concomitantly affects nuclear structure, lipid droplets (LD), organelle and cell growth. Here a fly miniscreen identified that Torsins affect these events via the NEP1R1-CTDNEP1 phosphatase complex. Further, Torsin homo-oligomerization rather than ATPase activity was key to function. NEP1R1-CTDNEP1 activates Lipin by dephosphorylation. We show that Torsin prevents CTDNEP1 from accumulating in the NE and excludes Lipin from the nucleus. Moreover, this repression of nuclear PA metabolism is required for interphase nuclear pore biogenesis. We conclude that Torsin is an upstream regulator of the NEP1R1-CTDNEP1/ Lipin pathway. This connects the ER/NE lumen with PA metabolism, and affects numerous cellular events including it has a previously unrecognized role in nuclear pore biogenesis.HighlightsNuclear envelope PA-DAG-TAG synthesis is independently regulated by Torsin and Torip/LAP1Torsin removes CTDNEP1 from the nuclear envelope and excludes Lipin from the nucleusExcess nuclear envelope NEP1R1-CTDNEP1/ Lipin activity impairs multiple aspects of NPC biogenesisNEP1R1-CTDNEP1/ Lipin inhibition prevents cellular defects associated withTOR1AandTOR1AIP1/ LAP1 disease
Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice
Authors: Botterill Justin J , Vinod K Yaragudri , Gerencer Kathleen J , Teixeira Cátia M , LaFrancois John J , Scharfman Helen E 
Published: July 2020

ABSTRACTThe dentate gyrus (DG) of the hippocampus is important for cognitive and affective behaviors. However, the circuits underlying these behaviors are unclear. DG mossy cells (MCs) have been a focus of attention because of their excitatory synapses on the primary DG cell type, granule cells (GCs). However, MCs also activate DG GABAergic neurons which inhibit GCs. We took advantage of specific methods and a gain- and loss-of function strategy with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to study MCs in diverse behaviors. Using this approach, manipulations of MCs could bidirectionally regulate behavior. The results suggest that inhibiting MCs can reduce anxiety-like behavior and improve cognitive performance. However, not all cognitive or anxiety-related behaviors were influenced, suggesting specific roles of MCs in some but not all types of cognition and anxiety. Notably, several behaviors showed sex-specific effects, with females often showing more pronounced effects than the males. We also used the immediate early gene c-Fos to address whether DREADDs bidirectionally regulated MC or GC activity. We confirmed excitatory DREADDs increased MC c-Fos. However, there was no change in GC c-Fos, consistent with MC activation leading to GABAergic inhibition of GCs. In contrast, inhibitory DREADDs led to a large increase in GC c-Fos, consistent with a reduction in MC excitation of GABAergic neurons, and reduced inhibition of GCs. Taken together, these results suggest that MCs regulate anxiety and cognition in specific ways. We also raise the possibility that cognitive performance may be improved by reducing anxiety.SIGNIFICANCE STATEMENTThe dentate gyrus (DG) has many important cognitive roles as well as being associated with affective behavior. This study addressed how a glutamatergic DG cell type called mossy cells (MCs) contributes to diverse behaviors, which is timely because it is known that MCs regulate the activity of the primary DG cell type, granule cells (GCs), but how MC activity influences behavior is unclear. We show, surprisingly, that activating MCs can lead to adverse behavioral outcomes, and inhibiting MCs have an opposite effect. Importantly, the results appeared to be task-dependent and showed that testing both sexes was important. Additional experiments indicated what MC and GC circuitry was involved. Taken together, the results suggest how MCs influence behaviors that involve the DG.
Crash landing ofVibrio choleraeby MSHA pili-assisted braking and anchoring in a viscoelastic environment
Authors: Zhang Wenchao , Luo Mei , Feng Chunying , Liu Huaqing , Zhang Hong , Bennett Rachel R. , Utada Andrew S. , Liu Zhi , Zhao Kun 
Published: July 2020

AbstractMannose-sensitive hemagglutinin (MSHA) pili and flagellum are critical for the surface attachment ofVibrio cholerae, the first step ofV. choleraecolonization on host surfaces. However, the cell landing mechanism remains largely unknown, particularly in viscoelastic environments such as the mucus layers of intestines. Here, combining the cysteine-substitution-based labelling method with single-cell tracking techniques, we quantitatively characterized the landing ofV. choleraeby directly observing both pili and flagellum of cells in a viscoelastic non-Newtonian solution consisting of 2% Luria-Bertani and 1% methylcellulose (LB+MC). The results show that MSHA pili are evenly distributed along the cell length and can stick to surfaces at any point along the filament. With such properties, MSHA pili are observed to act as a brake and anchor during cell landing which include three phases: running, lingering, and attaching. Importantly, loss of MSHA pili results in a more dramatic increase in mean path length in LB+MC than in 2% LB only or in 20% Ficoll solutions, indicating that the role of MSHA pili during cell landing is more apparent in viscoelastic non-Newtonian fluids than viscous Newtonian ones. Our work provides a detailed picture of the landing dynamics ofV. choleraeunder viscoelastic conditions, which can provide insights into ways to better controlV. choleraeinfections in real mucus-like environment.
Higher order thalamus encodes correct goal-directed action
Authors: LaTerra D. , Petryszyn S. , Rosier Marius , Palmer L.M. 
Published: July 2020

ABSTRACTThe thalamus is the gateway to the cortex. Cortical encoding of sensory information can therefore only be understood by considering the influence of thalamic processing on sensory input. Despite modulating sensory processing, little is known about the role of the thalamus during sensory-based behavior, let alone goal-directed behavior. Here, we use two-photon Ca2+imaging, patch-clamp electrophysiology and optogenetics to investigate the role of axonal projections from the posteromedial nucleus of the thalamus (POm) to the forepaw area of the primary somatosensory cortex (forepaw S1) during sensory processing and goal-directed behavior. We demonstrate that POm axons are active during tactile stimulus and increase activity specifically during the response and, to a lesser extent, reward epochs of a tactile goal-directed task. Furthermore, POm axons in forepaw S1 preferentially signaled correct behavior, with greatest activity during HIT responses. This activity is important for behavioral performance, as photoinhibition of archaerhodopsin-expressing neurons in the POm decreased overall behavioral success. Direct juxtacelluar recordings in the awake state illustrates POm neurons fire sustained action potentials during tactile stimulus. This tactile-evoked POm firing pattern was used during ChR2 photoactivation of POm axons in forepaw S1, revealing that action potentials in layer 2/3 (L2/3) pyramidal neurons are inhibited during sustained POm input. Taken together, POm axonal projections in forepaw S1 encode correct goal-directed active behavior, leading to GABAA-mediated inhibition of L2/3 pyramidal neurons.
Machine learning dimensionality reduction for heart rate n-variability (HRnV) based risk stratification of chest pain patients in the emergency department
Authors: Liu Nan , Chee Marcel Lucas , Koh Zhi Xiong , Leow Su Li , Wah Ho Andrew Fu , Guo Dagang , Hock Ong Marcus Eng 
Published: July 2020

AbstractBackgroundChest pain is among the most common presenting complaints in the emergency department (ED). Swift and accurate risk stratification of chest pain patients in the ED may improve patient outcomes and reduce unnecessary costs. Traditional logistic regression with stepwise variable selection has been used to build risk prediction models for ED chest pain patients. In this study, we aimed to investigate if machine learning dimensionality reduction methods can achieve superior performance than the stepwise approach in deriving risk stratification models.MethodsA retrospective analysis was conducted on the data of patients >20 years old who presented to the ED of Singapore General Hospital with chest pain between September 2010 and July 2015. Variables used included demographics, medical history, laboratory findings, heart rate variability (HRV), and HRnV parameters calculated from five to six-minute electrocardiograms (ECGs). The primary outcome was 30-day major adverse cardiac events (MACE), which included death, acute myocardial infarction, and revascularization. Candidate variables identified using univariable analysis were then used to generate the stepwise logistic regression model and eight machine learning dimensionality reduction prediction models. A separate set of models was derived by excluding troponin. Receiver operating characteristic (ROC) and calibration analysis was used to compare model performance.Results795 patients were included in the analysis, of which 247 (31%) met the primary outcome of 30-day MACE. Patients with MACE were older and more likely to be male. All eight dimensionality reduction methods marginally but non-significantly outperformed stepwise variable selection; The multidimensional scaling algorithm performed the best with an area under the curve (AUC) of 0.901. All HRnV-based models generated in this study outperformed several existing clinical scores in ROC analysis.ConclusionsHRnV-based models using stepwise logistic regression performed better than existing chest pain scores for predicting MACE, with only marginal improvements using machine learning dimensionality reduction. Moreover, traditional stepwise approach benefits from model transparency and interpretability; in comparison, machine learning dimensionality reduction models are black boxes, making them difficult to explain in clinical practice.