bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling drug combination effects via latent tensor reconstruction
Authors: Wang Tianduanyi , Szedmak Sandor , Wang Haishan , Aittokallio Tero , Pahikkala Tapio , Cichonska Anna , Rousu Juho
Published: April 2021

Abstract

Motivation

Combination therapies have emerged as a powerful treatment modality to overcome drug resistance and improve treatment efficacy. However, the number of possible drug combinations increases very rapidly with the number of individual drugs in consideration which makes the comprehensive experimental screening infeasible in practice. Machine learning models offer time- and cost-efficient means to aid this process by prioritising the most effective drug combinations for further pre-clinical and clinical validation. However, the complexity of the underlying interaction patterns across multiple drug doses and in different cellular contexts poses challenges to the predictive modelling of drug combination effects.

Results

We introducecomboLTR, highly time-efficient method for learning complex, nonlinear target functions for describing the responses of therapeutic agent combinations in various doses and cancer cell-contexts. The method is based on a polynomial regression via powerful latent tensor reconstruction. It uses a combination of recommender system-style features indexing the data tensor of response values in different contexts, and chemical and multi-omics features as inputs. We demonstrate thatcomboLTRoutperforms state-of-the-art methods in terms of predictive performance and running time, and produces highly accurate results even in the challenging and practical inference scenario where full dose-response matrices are predicted for completely new drug combinations with no available combination and monotherapy response measurements in any training cell line.

Availability and implementation

comboLTRcode is available athttps://github.com/aalto-ics-kepaco/ComboLTR

Contact

tianduanyi.wang@aalto.fi;juho.rousu@aalto.fi
An Artificial Intelligence and Telemedicine Based Screening Tool to Identify Glaucoma Suspects from Color Fundus Imaging
Authors: Bhuiyan Alauddin , Govindaiah Arun , Smith R Theodore
Published: April 2021

Backgrounds & Objective

Glaucomatous vision loss may be preceded by an enlargement of the cup-to-disc ratio (CDR). We propose to develop and validate an artificial intelligence based CDR grading system that may aid in effective glaucoma-suspect screening.

Design, Setting & Participants

1546 disc-centered fundus images were selected including all 457 images from the Retinal Image Database for Optic Nerve Evaluation dataset, and images randomly selected from the Age-Related EyeDisease Study, and Singapore Malay Eye Study to develop the system. First, a proprietary semi-automated software was used by an expert grader to quantify vertical CDR. Then, using CDR below 0.5 (not suspect) and CDR above 0.5 (glaucoma-suspect), deep learning architectures were used to train and test a binary classifier system.

Measurements

The binary classifier, with glaucoma-suspect as positive, is measured using sensitivity, specificity, accuracy, and AUC.

Results

The system achieved an accuracy of 89.67% (sensitivity, 83.33%; specificity, 93.89%; AUC, 0.93). For external validation, the Retinal Fundus Image database for Glaucoma Analysis dataset, which has 638 gradable quality images, was used. Here the model achieved an accuracy of 83.54% (sensitivity, 80.11%; specificity, 84.96%; AUC, 0.85).

Conclusions

Having demonstrated an accurate and fully automated glaucoma-suspect screening system that can be deployed on telemedicine platforms, we plan prospective trials to determine the feasibility of the system in primary care settings.
Evidence for a general neural signature of face familiarity
Authors: Dalski Alexia , Kovács Gyula , Ambrus Géza Gergely
Published: April 2021

We explored the neural signatures of face familiarity using cross-participant and cross-experiment decoding of event-related potentials, evoked by unknown and experimentally familiarized faces from a set of experiments with different participants, stimuli, and familiarization-types. Participants were either familiarized perceptually, via media exposure, or by personal interaction. We observed significant cross-experiment familiarity decoding involving all three experiments, predominantly over posterior and central regions of the right hemisphere in the 270 – 630 ms time window. This shared face familiarity effect was most prominent between the Media and Personal, as well as between the Perceptual and Personal experiments. Cross-experiment decodability makes this signal a strong candidate for a general neural indicator of face familiarity, independent of familiarization methods and stimuli. Furthermore, the sustained pattern of temporal generalization suggests that it reflects a single automatic processing cascade that is maintained over time.

Highlights

We investigated if a general neural signature of face familiarity exist

A cross-experiment decoding analysis of EEG data was used

The analysis involved perceptual, media and personal familiarization methods

We found a preserved pattern of familiarity decoding across experiments between 270 and 630 ms post-stimulus

This signature is consistent with previous reports on face familiarity effects
Ubiquity of the SymbiontSerratia symbioticain the Aphid Natural Environment: Distribution, Diversity and Evolution at a Multitrophic Level
Authors: Pons Inès , Scieur Nora , Dhondt Linda , Renard Marie-Eve , Renoz François , Hance Thierry
Published: April 2021

Bacterial symbioses are significant drivers of insect evolutionary ecology. However, despite recent findings that these associations can emerge from environmentally derived bacterial precursors, there is still little information on how these potential progenitors of insect symbionts circulates in the trophic systems. The aphid symbiontSerratia symbioticarepresents a valuable model for deciphering evolutionary scenarios of bacterial acquisition by insects, as its diversity includes intracellular host-dependent strains as well as gut-associated strains that have retained some ability to live independently of their hosts and circulate in plant phloem sap. These strains represent a potential reservoir for the emergence of new and more intimate symbioses. Here, we conducted a field study to examine the distribution and diversity ofS. symbioticafound in aphid populations, as well as in different compartments of their surrounding environment. A total of 250 aphid colonies, 203 associated insects, and 161 plant samples associated with aphid colonies were screened forS. symbiotica. Twenty percent of aphids were infected withS. symbiotica, and the symbiont includes a wide diversity of strains with varied tissue tropism corresponding to different lifestyle. We also showed that the prevalence ofS. symbioticais influenced by seasonal temperatures. For the first time, we found thatS. symbioticawas present in non aphid species and in host plants, and that the prevalence of the bacterium in these samples was higher when associated aphid colonies were infected. Furthermore, phylogenetic analyses suggest the existence of horizontal transfers between the different trophic levels examined. These results provide a completely new picture of the ubiquity of an insect symbiont in nature. They suggest that ecological interactions promote the dissemination of strains that are still free-living and poorly specialized, and for which plants are a proabable reservoir for the acquisition of new bacterial partners in insects.
Chemical phylogenetics of the staphylococcal quorum sensing landscape
Authors: Gless Bengt H. , Bejder Benjamin S. , Vitolo Ludovica , Marques Leonor , Andersen Paal S. , Bojer Martin S. , Ingmer Hanne , Olsen Christian A.
Published: April 2021

Staphylococci utilize secreted autoinducing peptides (AIPs) to regulate group behaviour through a process called quorum sensing (QS). Here, we survey the QS interaction landscape within theStaphylococcusgenus by assembling a unique compound collection, comprising all the currently known AIPs. These ribosomally synthesized and posttranslationally modified peptides (RiPPs) were obtained by chemical synthesis and mapping of their ability to modulate QS was evaluated using reporter strains of common human and animal colonizing pathogens (S. aureus, S. epidermidis, S. lugdunensis). The resulting map of >200 native QS interactions provides a holistic view of nodes that contribute to the complex signalling network within theStaphylococcusgenus. This overview reveals surprising cross-species QS induction and identify the first pan-inhibitory AIP, which is then shown to attenuate MRSA induced skin infection in a mouse model. Our results expose a complex universe of possible staphylococcal interactions and provide further impetus for development of therapeutics based on QS modulators targeting antibiotic resistant pathogens.
Genome organisation and evolution of a eukaryotic nicotinate co-inducible pathway
Authors: Bokor Eszter , Flipphi Michel , Kocsubé Sándor , Ámon Judit , Vágvölgyi Csaba , Scazzocchio Claudio , Hamari Zsuzsanna
Published: April 2021

InAspergillus nidulansa regulon including 11hxngenes (hxnS, T, R, P, Y, Z, X, W, V, MandN) is inducible by a nicotinate metabolic derivative, repressible by ammonium and under stringent control of the nitrogen-state sensitive GATA factor AreA and the specific transcription factor HxnR. This is the first report in a eukaryote of the genomic organisation of a possibly complete pathway of nicotinate utilisation. InA. nidulansthe regulon is organised in three distinct clusters, this organisation is variable in theAscomycota. In somePezizomycotinaspecies all the 11 genes map in a single cluster, in other in two clusters. This variable organisation sheds light on cluster evolution. Instances of gene duplication, followed by, or simultaneous with, integration in the cluster; partial or total cluster loss; horizontal gene transfer of several genes, including an example of whole cluster re-acquisition inAspergillusof sectionFlaviwere detected, together with the incorporation in some clusters of genes not found in theA. nidulansco-regulated regulon, which underlie both the plasticity and the reticulate character of metabolic cluster evolution. This study provides a comprehensive phylogeny of six members of the cluster across representatives of allAscomycotaclasses.
DNMT3A-dependent DNA methylation is required for spermatogonial stem cells to commit to spermatogenesis
Authors: Dura Mathilde , Teissandier Aurélie , Armand Mélanie , Barau Joan , Bonneville Lorraine , Weber Michael , Baudrin Laura G. , Lameiras Sonia , Bourc’his Deborah
Published: April 2021

DNA methylation plays a critical role in spermatogenesis, as evidenced by the male sterility of DNA methyltransferase (DNMT) mutant mice. Here, we report a striking division of labor in the establishment of the methylation landscape of male germ cells and its functions in spermatogenesis: while DNMT3C is essential for preventing retrotransposons from interfering with meiosis, DNMT3A broadly methylates the genome—at the exception of DNMT3C-dependent retrotransposons—and controls spermatogonial stem cell (SSC) plasticity. By reconstructing developmental trajectories through single-cell RNA-seq and by profiling chromatin states, we found thatDnmt3Amutant SSCs can only self-renew and no longer differentiate due to spurious enhancer activation that enforces an irreversible stem cell gene program. We therefore provide a novel function for DNA methylation in male fertility: the epigenetic programming of SSC commitment to differentiation and to life-long spermatogenesis supply.
Replication timing analysis in polyploid cells reveals Rif1 uses multiple mechanisms to promote underreplication in Drosophila
Authors: Das Souradip , Caballero Madison , Kolesnikova Tatyana , Zhimulev Igor , Koren Amnon , Nordman Jared
Published: April 2021

Regulation of DNA replication and copy number are necessary to promote genome stability and maintain cell and tissue function. DNA replication is regulated temporally in a process known as replication timing (RT). Rif1 is key regulator of RT and has a critical function in copy number control in polyploid cells. In a previous study (Munden et al., 2018), we demonstrated that Rif1 functions with SUUR to inhibit replication fork progression and promote underreplication (UR) of specific genomic regions. How Rif1-dependent control of RT factors into its ability to promote UR is unknown. By applying a computational approach to measure RT in Drosophila polyploid cells, we show that SUUR and Rif1 have differential roles in controlling UR and RT. Our findings reveal that Rif1 functions both upstream and downstream of SUUR to promote UR. Our work provides new mechanistic insight into the process of UR and its links to RT.
Differential learning by native versus invasive predators to avoid distasteful cleaning mutualists
Authors: Tuttle Lillian J. , Lamb Robert W. , Stringer Allison L.
Published: April 2021

Cleaning symbioses on coral reefs are mutually beneficial interactions between two individuals, in which a ‘cleaner’ removes and eats parasites from the surface of a ‘client’ fish. A suite of behavioural and morphological traits of cleaners signal cooperation with co‐evolved species, thus protecting the cleaner from being eaten by otherwise predatory clients. However, it is unclear whether cooperation between cleaners and predatory clients is innate or learned, and therefore whether an introduced predator might consume, cooperate with or alter the behaviour of cleaners.

We explored the role of learning in cleaning symbioses by comparing the interactions of native cleaner fishes with both naïve and experienced, non‐native and native fish predators. In so doing, we tested the vulnerability of the predominant cleaners on Atlantic coral reefs, cleaning gobies (Elacatinus spp.), to the recent introduction of a generalist predator, the Indo‐Pacific red lionfish (Pterois volitans).

Naïve juveniles of both invasive (P. volitans) and native predators (Cephalopholis spp. groupers) initially attacked cleaning gobies and hyperventilated from a putative toxin on the gobies' skin during laboratory experiments. After one to five such encounters, invasive lionfish often approached the cleaner closely, then turned away without striking. Consistent with learned avoidance, invasive lionfish rarely interacted with cleaning gobies in the wild, either antagonistically or cooperatively, and did not affect gobies' abundance. Native predators showed little evidence of learning during early encounters; they repeatedly attacked the cleaner during laboratory experiments and hyperventilated less violently than did lionfish. However, consistent with learned cooperation, native predators rarely antagonised and were frequently cleaned by gobies in the wild.

We demonstrated that rapid, learned avoidance protects a distasteful cleaning mutualist from an invasive predator. The behavioural plasticity of this invader likely contributes to its success across its invaded range. Additionally, our results suggest that the cleaner's chemical defence most likely evolved as a way to deter predation and reinforce cooperation with naïve individuals of native species.
Fine‐scale plant defence variability increases top‐down control of an herbivore
Authors: Paul Ryan L. , Pearse Ian S. , Ode Paul J.
Published: April 2021

Herbivore populations are regulated by a combination of plant defences and natural enemies. While plant defence can suppress herbivore populations, these defences can also adversely affect natural enemies, thereby releasing herbivores from top‐down control.

Over their life spans, herbivores and their natural enemies may experience substantial variation in plant defence. Recent studies have demonstrated that individual herbivores feeding on diets containing variable concentrations of plant toxins suffer substantially reduced fitness compared to herbivores feeding on a constant toxin concentration, even when both groups of herbivores experience equivalent means. However, the impacts of defence variability on natural enemies and top‐down control of herbivores are unknown.

Using artificial diets, we independently manipulated the mean concentration and variation of a plant toxin experienced by individual Trichoplusia ni caterpillars and its parasitoid Copidosoma floridanum. Additionally, by combining the performance of individual caterpillars on different constant diet concentrations of toxin, we were able to estimate the effect of toxin variability between herbivores using nonlinear averaging.

Increases in the mean toxin concentration in the diet of parasitized T. ni hosts decreased the fitness of C. floridanum, while variance in individual diets did not impact parasitoid fitness, even though both mean and variance decreased the fitness of T. ni caterpillars. Increased variability in encountered plant defences suppressed individual herbivore fitness with no perceptible cost to top‐down control. At the population level, however, increased variability between individual herbivore diets decreased the success of parasitoids relative to herbivores, thus reducing the strength of top‐down control.

Our study highlights the importance of defence variability at different scales in regulating herbivore performance. Variability in plant defence has the potential to reduce herbivore populations through a combination of bottom‐up and top‐down effects, but only at small spatial scales experienced by individual herbivores.

A free Plain Language Summary can be found within the Supporting Information of this article.
Thermal evolution ameliorates the long‐term plastic effects of warming, temperature fluctuations and heat waves on predator–prey interaction strength
Authors: Wang Ying‐Jie , Sentis Arnaud , Tüzün Nedim , Stoks Robby
Published: April 2021

How thermal evolution may affect trophic interactions and its implications for trophic system stability remains unstudied. To advance insights in how global warming shapes trophic interactions, we need to consider besides increases in mean temperatures, also daily thermal fluctuations (DTF) and heat waves (HW), and how their effects are modulated by thermal evolution.

Using a common‐garden approach, we tested how each thermal factor affected predator metabolic rate and functional response parameters, and used these responses to predict long‐term predator–prey interaction strength between larvae of the damselfly Ischnura elegans and the water flea Daphnia magna. Using high‐ and low‐latitude predator populations with the latter being exposed to higher mean temperatures, higher DTF and more frequent HW, we assessed the potential impact of thermal evolution at the high latitude using a space‐for‐time substitution.

In line with thermal adaptation, growth rates were faster and handling times shorter in low‐latitude compared to high‐latitude larvae at 24°C while the opposite was true at 20°C. Warming weakened the long‐term interaction strength, except for the high‐latitude trophic system at DTF and HW where plastic responses therefore may not stabilize the high‐latitude system. This extends the emerging insight that temperature variation may make ectotherms more vulnerable to warming. The contributions of metabolic rate, search rate and handling time in shaping thermal effects on interaction strength differed between latitudes. A key finding was that thermal evolution may further weaken the long‐term interaction strength of the high‐latitude trophic system under increases in mean temperatures, even at DTF and potentially also at HW.

Our results underscore the importance of daily thermal fluctuations and heat waves in shaping predator–prey interactions, and may suggest an overall stabilizing contribution of predator thermal evolution ameliorating thermal plastic effects on food web stability.

A free Plain Language Summary can be found within the Supporting Information of this article.
Sweet spheres: succession and CAZyme expression of marine bacterial communities colonizing a mix of alginate and pectin particles
Authors: Bunse Carina , Koch Hanna , Breider Sven , Simon Meinhard , Wietz Matthias
Published: April 2021

Polysaccharide particles are important substrates and microhabitats for marine bacteria. However, substrate‐specific bacterial dynamics in mixtures of particle types with different polysaccharide composition, as likely occurring in natural habitats, are undescribed. Here, we studied the composition, functional diversity and gene expression of marine bacterial communities colonizing a mix of alginate and pectin particles. Amplicon, metagenome and metatranscriptome sequencing revealed that communities on alginate and pectin particles significantly differed from their free‐living counterparts. Unexpectedly, microbial dynamics on alginate and pectin particles were similar, with predominance of amplicon sequence variants (ASVs) from Tenacibaculum, Colwellia, Psychrobium and Psychromonas. Corresponding metagenome‐assembled genomes (MAGs) expressed diverse alginate lyases, several colocalized in polysaccharide utilization loci. Only a single, low‐abundant MAG showed elevated transcript abundances of pectin‐degrading enzymes. One specific Glaciecola ASV dominated the free‐living fraction, possibly persisting on particle‐derived oligomers through different glycoside hydrolases. Elevated ammonium uptake and metabolism signified nitrogen as an important factor for degrading carbon‐rich particles, whereas elevated methylcitrate and glyoxylate cycles suggested nutrient limitation in surrounding waters. The bacterial preference for alginate, whereas pectin primarily served as colonization scaffold, illuminates substrate‐driven dynamics within mixed polysaccharide pools. These insights expand our understanding of bacterial niche specialization and the biological carbon pump in macroalgae‐rich habitats.
Grammatical Encoding of Discourse Structure: A Case Study of The Arabic Discourse Particle Tara
Authors: Jarrah Marwan , Harb Mustafa
Published: April 2021

This study shows that the discourse particle tara in Jordanian Arabic identifies whether its utterance presents new or given information. In other words, there exists a relation between the presence of this particle (i.e. its position) and the type of information packaging of its utterance. When tara appears utterance‐initially, the accompanying utterance is presented as being in sentence focus (i.e. as all‐new). By contrast, when tara appears utterance‐finally, the accompanying utterance is presented as all‐given, and the hearer in such cases is instructed to pay attention to the content of the utterance which he/she should be previously aware of, from the speaker’s perspective. Additionally, this paper shows that tara can be used as a topic marker when it appears utterance‐internally. In such cases, tara is preceded by the element(s) expressing Referential Topic(s) (RTop) which convey the shared and anaphoric information with respect to the interlocutors’ mental state and previous discourse.
Five‐year impact of Medicare Part D coverage gap reform on drug expenditures and utilization
Authors: Park Joohyun , Look Kevin A.
Published: April 2021

Objective

To estimate the impact of the Medicare Part D coverage gap reform under the Affordable Care Act (ACA) on the utilization of and expenditures for prescription drugs within the first five years of the policy's implementation.

Data Sources

2008‐2015 Medicare Current Beneficiary Survey (MCBS).

Study Design

We used a difference‐in‐differences approach to estimate the year‐by‐year changes in prescription drug use and expenditures before (2006‐2010) and after (2011‐2015) the ACA’s Part D coverage gap reform between Part D beneficiaries not receiving the Low‐Income Subsidy (LIS) and those receiving the LIS.

Data Collection

The study sample included Part D beneficiaries (a) aged 65 years or older; (b) not disabled or having end‐stage renal disease; (c) continuously enrolled in a Part D plan (d) having at least one prescription fill in a given year. Survey‐reported and administrative Part D events data in the MCBS were used for the analyses.

Principal Findings

After the ACA reform, annual out‐of‐pocket drug spending significantly decreased by $88 (P < .01) among non‐LIS beneficiaries compared to LIS beneficiaries, with growing decreases over time (average decreases of $41 in 2011, $49 in 2012, $105 in 2013, and $135 in 2015, P < .01 or <.05). Changes in out‐of‐pocket costs were largely driven by significant decreases among brand‐name drugs (overall decrease of $106, P < .01). Despite significantly reduced out‐of‐pocket spending, there were no significant changes in the overall number of 30‐day drug fills and total drug spending; however, changes in the use of brand‐name and generic drugs were seen after the ACA (increase of 1.9 fills for brand‐name drugs and decrease of 2.3 fills for generic drug in 2015, P < .05).

Conclusions

The ACA coverage gap reform has helped to reduce the out‐of‐pocket drug cost burden for beneficiaries, although it had no noticeable impact on drug use or total drug spending.
Gender disparity in bipolar disorder diagnosis in the United States: A retrospective analysis of the 2005–2017 MarketScan Commercial Claims database
Authors: Liu Guodong , Kong Lan , Baweja Ritika , Ba Djibril , Saunders Erika F. H.
Published: April 2021

Objective

To examine gender disparities in the diagnosis of bipolar disorder (BD) within a privately insured population in the United States and investigate potential contributing factors for these gender differences.

Methods

This retrospective cohort study utilized 2005–2017 claims data from the MarketScan® Commercial Claims and Encounters database. The study cohort included subjects, aged 10–64 years, who had a minimum of 1‐year continuous insurance coverage and no record of a BD diagnosis before cohort entry. We examined the gender difference in BD diagnosis rate, overall and by subgroups. We then used Cox regression models to evaluate the gender effect on time to first BD diagnosis, and the potential moderators of gender effect.

Results

The study cohort consisted of 97,193,443 subjects; 0.45% of subjects were diagnosed with BDs after cohort entry with males having a lower diagnosis rate than females (0.36% vs. 0.54%). The Cox regression analysis indicated that males were less likely to be diagnosed with BDs (unadjusted Hazard Ratio, HR [95% CI]: 0.69 [0.68–0.69]) and gender difference remained significant after adjusting for demographics, comorbidity and healthcare utilizations (adjusted HR [95% CI]: 0.77 [0.76–0.77]). Gender disparity was consistently strong among most age groups, but varied in other demographic subgroups.

Conclusions

Even though the prevalence of BDs is approximately equal between genders in the general population, our study found a much lower diagnosis rate in men compared to women for a privately insured U.S. population. Future studies aimed at identifying and understanding the barriers to diagnosis of BDs in men are warranted.
Investigating the role of self‐control beliefs in predicting exercise behaviour: A longitudinal study
Authors: Kaushal Navin , Bérubé Béatrice , Hagger Martin S. , Bherer Louis
Published: April 2021

Background

Engaging in exercise behaviour regularly requires a repeated investment of resources to reap the health benefits. An individual’s self‐control resources, when performing a behaviour can be perceived as being recharged or depleted. The investigation on how self‐control beliefs resources predict exercise behaviour is very limited in the literature. The purpose of this study was to understand how self‐control beliefs predict exercise behaviour across time in a physical activity model.

Methods

Participants (N = 161) were a sample of adults recruited across twelve gyms and recreation centres in a large city. Participants completed surveys across five months. Data were analysed using a multilevel structural equation model with participants (level 2) nested within time (level 1).

Results

Behaviour was found to be a function of intention, habit, and planning. Specifically, planning moderated the intention‐behaviour relationship, where those who scored higher on planning engaged in more exercise. Self‐control beliefs functioned as a proximal predictor of autonomous motivation and predicted habit, and intention when accounting for total effects.

Conclusions

Self‐control beliefs played a pivotal role in supporting recognized exercise determinants. Exercise‐focussed interventions that help participants strengthen their beliefs as recharging and reduce depletion beliefs could be beneficial for promoting regular exercise.
Is Anyone There? Use of the Telephone and Use of the Couch
Authors: Murdin Lesley
Published: April 2021

Many therapists have been using the telephone for analytic sessions during the Covid 19 pandemic. This paper considers the ways in which the use of the telephone resembles the use of the couch and revisits the value of the couch in order to assess the value of the telephone. The questions raised are whether analytic therapists still find the use of the couch helpful, and if so why. This is then linked to the experience of using only the telephone. The paper considers the ways in which the two techniques increase or diminish shame and the willingness to disclose difficult material. An anonymized clinical illustration is used of a woman who began in face‐to‐face work with a purely practical problem, but in telephone sessions was able to acknowledge her need to understand her own mental state in order to be able to change at a deeper level. Conclusions are drawn about the positive usefulness of the telephone in contrast with the view that it is just the best that we can do in some circumstances.
Curious Objects: How Visual Complexity Guides Attention and Engagement
Authors: Sun Zekun , Firestone Chaz
Published: April 2021

Some things look more complex than others. For example, a crenulate and richly organized leaf may seem more complex than a plain stone. What is the nature of this experience—and why do we have it in the first place? Here, we explore how object complexity serves as an efficiently extracted visual signal that the object merits further exploration. We algorithmically generated a library of geometric shapes and determined their complexity by computing the cumulative surprisal of their internal skeletons—essentially quantifying the “amount of information” within each shape—and then used this approach to ask new questions about the perception of complexity. Experiments 1–3 asked what kind of mental process extracts visual complexity: a slow, deliberate, reflective process (as when we decide that an object is expensive or popular) or a fast, effortless, and automatic process (as when we see that an object is big or blue)? We placed simple and complex objects in visual search arrays and discovered that complex objects were easier to find among simple distractors than simple objects are among complex distractors—a classic search asymmetry indicating that complexity is prioritized in visual processing. Next, we explored the function of complexity: Why do we represent object complexity in the first place? Experiments 4–5 asked subjects to study serially presented objects in a self‐paced manner (for a later memory test); subjects dwelled longer on complex objects than simple objects—even when object shape was completely task‐irrelevant—suggesting a connection between visual complexity and exploratory engagement. Finally, Experiment 6 connected these implicit measures of complexity to explicit judgments. Collectively, these findings suggest that visual complexity is extracted efficiently and automatically, and even arouses a kind of “perceptual curiosity” about objects that encourages subsequent attentional engagement.
Counterexample Search in Diagram‐Based Geometric Reasoning
Authors: Hamami Yacin , Mumma John , Amalric Marie
Published: April 2021

Topological relations such as inside, outside, or intersection are ubiquitous to our spatial thinking. Here, we examined how people reason deductively with topological relations between points, lines, and circles in geometric diagrams. We hypothesized in particular that a counterexample search generally underlies this type of reasoning. We first verified that educated adults without specific math training were able to produce correct diagrammatic representations contained in the premisses of an inference. Our first experiment then revealed that subjects who correctly judged an inference as invalid almost always produced a counterexample to support their answer. Noticeably, even if the counterexample always bore a certain level of similarity to the initial diagram, we observed that an object was more likely to be varied between the two drawings if it was present in the conclusion of the inference. Experiments 2 and 3 then directly probed counterexample search. While participants were asked to evaluate a conclusion on the basis of a given diagram and some premisses, we modulated the difficulty of reaching a counterexample from the diagram. Our results indicate that both decreasing the counterexample density and increasing the counterexample distance impaired reasoning performance. Taken together, our results suggest that a search procedure for counterexamples, which proceeds object‐wise, could underlie diagram‐based geometric reasoning. Transposing points, lines, and circles to our spatial environment, the present study may ultimately provide insights on how humans reason about topological relations between positions, paths, and regions.
The Development of Cognitive Reflection in China
Authors: Gong Tianwei , Young Andrew G. , Shtulman Andrew
Published: April 2021

Cognitive reflection is the tendency to override an intuitive response so as to engage in the reflection necessary to derive a correct response. Here, we examine the emergence of cognitive reflection in a culture that values nonanalytic thinking styles, Chinese culture. We administered a child‐friendly version of the cognitive reflection test, the CRT‐D, to 130 adults and 111 school‐age children in China and compared performance on the CRT‐D to several measures of rational thinking (belief bias syllogisms, base rate sensitivity, denominator neglect, and other‐side thinking) and normative thinking dispositions (actively open‐minded thinking and need for cognition). The CRT‐D was a significant predictor of rational thinking and normative thinking dispositions in both children and adults, as previously found in American samples. Adults’ performance on the CRT‐D correlated with their performance on the original CRT, and children's performance on the CRT‐D predicted rational thinking and normative thinking dispositions even after adjusting for age. These results demonstrate that cognitive reflection, rational thinking, and normative thinking dispositions converge even in a culture that emphasizes holistic, nonanalytic reasoning.
Harnessing pluripotent stem cells as models to decipher human evolution
Authors: Dannemann Michael , Gallego Romero Irene
Published: April 2021

The study of human evolution, long constrained by a lack of experimental model systems, has been transformed by the emergence of the induced pluripotent stem cell (iPSC) field. iPSCs can be readily established from noninvasive tissue sources, from both humans and other primates; they can be maintained in the laboratory indefinitely, and they can be differentiated into other tissue types. These qualities mean that iPSCs are rapidly becoming established as viable and powerful model systems with which it is possible to address questions in human evolution that were until now logistically and ethically intractable, especially in the quest to understand humans' place among the great apes, and the genetic basis of human uniqueness. In this review, we discuss the key lessons and takeaways of this nascent field; from the types of research, iPSCs make possible to lingering challenges and likely future directions. We provide a comprehensive overview of how the seemingly unlikely combination of iPSCs and explicit evolutionary frameworks is transforming what is possible in our understanding of humanity's past and present.
Trypsinogen and chymotrypsinogen: the mysterious hyper‐reactivity of selected cysteines is still present after their divergent evolution
Authors: Cattani Giada , Bocedi Alessio , Gambardella Giorgia , Iavarone Federica , Boroumand Mozhgan , Castagnola Massimo , Ricci Giorgio
Published: April 2021

An enigmatic and never described hyper‐reactivity of most of the cysteines resident in the reduced, molten globule‐like intermediate of a few proteins has been recently discovered. In particular, all ten cysteines of chymotrypsinogen showed hundred times increased reactivity against hydrophobic reagents. A single cysteine (Cys1) was also found thousand times more reactive toward GSSG, making speculate that a single glutathionylation could represent the primordial event of its oxidative folding. In the present study, we compare these kinetic properties with those present in trypsinogen taken in its reduced, molten globule‐like intermediate and identify the origin of these unusual properties. Despite the divergent evolution of these two proteins, the different amount of disulfides and the very different 3D localization of three disulfides, their hyper‐reactivity toward hydrophobic thiol reagents and disulfides is very similar. Mass spectrometry identifies two cysteines in trypsinogen, Cys148 and Cys197, 800 times more reactive toward GSSG than an unperturbed protein cysteine. These results point toward a stringent and accurate preservation of these peculiar kinetic properties during a divergent evolution suggesting some important role, which at the present can only be hypothesized. Similar extraordinary hyper‐reactivity has been found also in albumin, ribonuclease, and lysozyme confirming that it cannot be considered a kinetic singularity of a single protein. Interestingly, the very flexible and fluctuating structures like those typical of the molten globule status prove capable of enabling sophisticated actions typical of enzymes such as binding to GSSG with relevant specificity and high affinity (KD = 0.4 mm) and accelerating the reaction of its cysteines by thousands of times.
Population structure of the European conger Conger conger from the mid‐North Atlantic Ocean inferred from bathymetric distribution, length composition and movement patterns analyses
Authors: Medeiros‐Leal Wendell , Santos Régis , Novoa‐Pabon Ana , Silva Hélder , Pinho Mario
Published: April 2021

Information about the population structure of Conger conger (L.) is scarce, being a limiting factor for fisheries assessment. To make available important baseline information and to test the hypothesis that the population in the mid‐North Atlantic (Azores region) represents a fishery management unit, fishery‐dependent and survey data relating to bathymetric distribution, length composition and movement patterns were examined. Fishing impacts were also evaluated using abundance and size trends over the last 25 years. The greatest abundance was in depths between 300 and 600 m. Sizes ranged from 14 to 260 cm, with larger individuals around seamounts. Tagging data showed a strong sedentary behaviour. Results combined with previous genetic and otolith studies indicated the stock in the Azores may represent a self‐contained population. Abundance and size trends were stable, but the species is considered vulnerable to overfishing due to its biological characteristics. Monitoring and adequate rational resource management are of utmost importance.
A comparative study on habitat models for adult bigeye tuna in the Indian Ocean based on gridded tuna longline fishery data
Authors: Zhang Tianjiao , Song Liming , Yuan Hongchun , Song Bo , Ebango Ngando Narcisse
Published: April 2021

Using the gridded fishery data to estimate the habitat preferences of bigeye tuna (Thunnus obesus) in the Indian Ocean is challenging, as it is still not clear what type of model is appropriate to make reliable habitat predictions. In this study, we tested two classes of habitat models: Generalized Additive Models (including Gaussian distribution GAM, Poisson distribution GAM, Negative Binomial distribution GAM, Tweedie class distribution GAM, and Zero‐inflated distribution GAM) and Maximum Entropy Model (MaxEnt) for forecasting the habitat of bigeye tuna in the Indian Ocean, using the 5°×5° monthly gridded fishery data from 2008 to 2015 provided by Indian Ocean Tuna Commission (IOTC) and the environmental factors (i.e., the vertical temperature, salinity, dissolved oxygen concentration, thermocline depth, vertical shear of ocean current, concentration of sea surface chlorophyll‐a (chl‐a), and the eddy kinetic energy (EKE)). We compared the models’ fitting ability, predictive performance, predicted results, and the ecological interpretation within the models. The results showed (1) GAMs provided better model fit and predictive performance than MaxEnt; (2) GA‐GAM showed the best model fit performance by using the log transformation of the standardized CPUE as response variable; (3) TW‐GAM was suitable for predicting the habitat of adult bigeye tuna with the over‐dispersed fishery datasets. (4) Results suggested that the vertical temperature, dissolved oxygen concentration, and thermocline depth could be used as reliable predictors in forecasting the spatial‐temporal distribution of the adult bigeye tuna in the Indian Ocean.
Sex effects for the interaction of dopamine related genetic variants for COMT and BDNF on declarative memory performance
Authors: Van der Auwera Sandra , Terock Jan , Teumer Alexander , Schomerus Georg , Homuth Georg , Grabe Hans J.
Published: April 2021

Genetic factors are assumed to contribute to memory performance, especially genes affecting the dopaminergic neurotransmission. We aimed to evaluate leading functional genetic variants of the dopamine system, Catechol‐O‐methyltransferase (COMT) SNP rs4680 and Brain‐derived neurotropic factor (BDNF) SNP rs6265, previously found to be associated with memory performance. In two independent general population cohorts (total N = 5937) we investigated direct and interaction effects between COMT and BDNF SNPs on declarative memory performance. We found significant two‐way interactions for COMT and BDNF in both cohorts but no direct genetic effects. Sensitivity analyses revealed that an interaction between COMT and BDNF was mainly carried by females. While direct associations of COMT and BDNF on memory have been reported previously, we could demonstrate that the interaction of COMT and BDNF is sex‐dependent and more complex and needs further investigation. Our results could be demonstrated in two independent cohorts of valuable size.
Preparation of Zr4+ doped calcium hexaaluminate with improved slag penetration resistance
Authors: Guo Chunyu , Wang Enhui , Hou Xinmei , Kang Junyi , Yang Tao , Liang Tongxiang , Bei Guoping
Published: April 2021

Aiming to improve the density of calcium hexaaluminate (CA6), Zr4+ doped CA6 with the structural formula of CaAl11.73◊0.25Zr0.02O18.41◊0.59 (CaAl11.73Zr0.02O18.41) was successfully synthesized at 1600℃ for 4 h in air. The effect of Zr4+ doping on the crystal structure of CA6 was investigated using first principle calculation, structure refinement in combination with experimental characterization. The results suggest that Zr4+ prefers to substitute the Al3+ at Al3 site, which can increase the lattice parameter of c‐axis and the amount of Al vacancies. The average thickness of Zr4+ doped CA6 is increased by approximate 36% in comparison with the pure one. In addition, molecular dynamics (MD) simulation indicates that Zr4+ doping can reduce the wettability of CA6 to slag to some extent. The reaction test method was carried out and it shows that CA6 with Zr4+ doping possesses better slag penetration resistance. Based on this, the reaction mechanism is also discussed.
Economic evaluation of workplace health promotion interventions focused on Lifestyle: Systematic review and meta‐analysis
Authors: Vargas‐Martínez Ana M. , Romero‐Saldaña Manuel , De Diego‐Cordero Rocío
Published: April 2021

Aim

To identify and evaluate randomized clinical trials focusing on economic evaluation of workplace health promotion (WHP) interventions based on healthy lifestyles, physical activity and nutrition.

Design

A systematic review and meta‐analysis was carried out between March and May 2019, following the PRISMA statement.

Data Sources

The literature search was conducted on Cochrane Library, Scopus, WOS and Medline databases.

Review Methods

The quality appraisal included the overall risk of bias (Cochrane Collaboration tool), the quality of the evidence (GRADEpro) and the quality of the health economic analysis (QHES instrument).

Results

Of the 15 studies selected, 3 were interventions based on nutrition, 11 were focused on lifestyle and only one on physical activity. Given the heterogeneity of included studies, it was decided to do a subgroup analysis. For the weight loss (n = 5 studies), a general increase of 0.56 Kg (95% CI = 0.76, 0.84) I2 = 99.41%, and for the Quality‐adjusted Life Years achieved (n = 5 studies) a very small increase of 0.003 (95% CI = 0.002, 0.004) I2 = 99.25%, were observed.

Conclusions

The implementation of lifestyle interventions in the workplace has proven to be cost‐effective for both employers and society.

Impact

What problem did the study address?There are few studies aimed at evaluating the efficiency of WHP interventions. However, those that identify and assessing interventions related to lifestyle are particularly scarce, despite the evidence showing that these researchers improve the quality of care of occupational health.

What were the main findings?This systematic review demonstrates the effectiveness of the WHP interventions, and in some cases, the efficiency of these interventions for both employers and society. Additional research in this area is necessary as well as the assessment of the cost‐effectiveness of such interventions.

Where and on whom will the research have an impact?To know the cost‐benefit of different WHP interventions allows more efficient management of resources, which helps to make political and business decisions, becoming healthier and safer workplaces.
Endoscopy training in COVID‐19: Challenges and hope for a better age
Authors: Koo Chieh Sian , Siah Kewin Tien Ho , Koh Calvin Jianyi
Published: April 2021

The COVID‐19 pandemic is a unique challenge that has disrupted endoscopy training. Initial infection control measures aimed at protecting patients and staff meant nonessential endoscopic activity was suspended in many countries. The decrease in elective caseload from the pandemic also reduced training numbers during this period. While hands‐on training took a backseat, more efforts were directed to didactic training of cognitive competencies. We review the literature describing the impact of COVID‐19 on endoscopy training and summarize key measures aimed at mitigating this effect. These include leveraging on web‐based didactic material and video‐conferences, increased use of simulation and models to hone technical competencies, and a shift in focus from numbers‐based accreditation to competency‐based accreditation. While COVID‐19 was hoped to be short‐lived, it is clear the impact is long‐lasting. Hence, it is crucial for training programs to take stock of how endoscopy training is evolving and use this opportunity to implement new paradigms into their endoscopic training curricula. COVID‐19 might just be the catalyst that transforms endoscopy training into a new digital era.
Housing and Tax Policy: Comment
Authors: GHIAIE HAMED , ROUILLARD JEAN‐FRANÇOIS
Published: April 2021

Alpanda and Zubairy (2016) examine the effects of permanent changes to four types of housing‐related tax policies in the context of a multiagent dynamic general equilibrium (DGE) model. They find long‐run tax multipliers that range from −2.21 to −1.53. However, we find an error in their codes that has a significant impact on the size of these multipliers. We correct their error and resimulate their model. The long‐run multipliers we find are reduced almost in half—they now range from −1.25 to −0.84. We also compute short‐run multipliers at a 20‐quarter horizon and find much lower multipliers, ranging between −0.14 and −0.02.