bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the use of preprints in dentistry
Authors: Sarkis-Onofre Rafael , Girotto Carolina , Agostini Bernardo Antonio
Published: July 2023

Objective:

This study aims to assess the use, impact, and dissemination of preprints in dentistry.

Methods:

This is a meta-research study with a cross-sectional design. We included preprints published in dentistry, regardless of the year of publication. Searches were performed in themedRxiv.organdPreprints.orgplatforms and restricted to English. One researcher extracted the data, and another researcher verified data consistency. The following data were extracted: year of publication, country of the corresponding author, number of abstract and full-text views and downloads, Altmetric attention score, whether the preprint was mentioned in other servers such as Twitter and Publons, number of mentions in other servers, number of citations in the Dimensions database, and whether the preprint had already been published in a peer-reviewed journal. If already published, we extracted the journal’s impact factor (JCR 2021) and the number of citations in the Dimensions database. We conducted a descriptive analysis of the extracted characteristics and explored relationships between metrics using the Spearman correlation.

Results:

We identified 276 preprints. Most of the studies were published between 2020 and 2022 (n= 229), especially those from ten countries. The most-cited preprint and published article are the same study. Only the correlation between the number of preprint citations and peer-reviewed article citations in the Dimensions database showed a large positive association (Spearman’s rho = 0.5809).

Conclusion:

Preprints gained popularity over the last several years due to the COVID-19 pandemic and reached a larger audience, especially on platforms such as Twitter.

Clinical Significance:

Preprint publishing allows faster dissemination of science for the benefit of society.
Changes in Masking Policies in US Healthcare Facilities in the First Quarter of 2023: Do COVID-19 Cases, Hospitalizations, or Local Political Preferences Predict Loosening Restrictions?
Authors: Miller Sarah L. , Prasad Vinay
Published: July 2023

Introduction

In the first half of 2023, many US healthcare facilities updated their policies on the required use of face masks by patients and employees. Despite statewide lifts of mask mandates in healthcare settings, the decisions by individual healthcare facilities have remained controversial and inconsistent. We sought to understand these decisions by examining COVID-19 case rates, hospitalization rates, and political affiliation, among counties where hospitals reported updated masking policies in news or social media posts.

Methods

We searched Twitter, Facebook, and Google for news stories related to changes in US healthcare facility masking policies between February 1st and April 30th, 2023. We extracted county-level COVID-19 cases and hospitalizations using data from the CDC and political affiliation was measured using the 2020 presidential election results. We performed logistic regression using COVID-19 cases, hospitalizations, and political affiliation as predictors and a complete lifting of masking requirements as the outcome.

Results

We found that the odds of lifting the mask requirement was not associated with COVID-19 cases (OR 1.00, 95% CI 0.97 - 1.02, p-value = 0.54), or hospitalizations (OR 1.06 95% CI 0.88-1.27, p-value = 0.33). We found that for every 10% increase in Republican votes in the 2020 presidential election, there was a 1.33 (95% CI 1.07 - 1.64, p-value = 0.01) increase in odds of having lifted masking requirements completely.

Discussion

We found that the odds of lifting the face mask requirement in healthcare facilities was not associated with COVID-19 cases or hospitalizations but was associated with county-level political affiliation. Our results raise the concern that public health measures may be increasingly seen as political gestures or a response to local political factors.
Implementation of risk triaging in primary healthcare facilities in Sub-Saharan Africa: A systematic review
Authors: Maskew Mhairi , Sande Linda Alinafe , Benade Mariet , Ntjiekelane Vinolia , Scott Nancy , Flynn David , Rosen Sydney
Published: July 2023

Background

One challenge facing treatment programs for HIV and other chronic conditions in sub-Saharan Africa (SSA) is how to target interventions to optimize retention in care and other outcomes. Most efforts to target interventions have identified predictive features among high risk patients after negative outcomes have already been observed. An alternative for identifying patients at high risk of negative outcomes is “risk triaging,” or identifying vulnerable or higher risk patients before they experience an interruption in care or other negative outcome. We conducted a systematic review of the use of risk triaging tools at the primary healthcare (PHC) level in SSA.

Methods

We searched PubMed and other databases for publications after 1 January 2012 that reported development or implementation of risk triaging tools for PHC use in SSA. We extracted information on three outcomes: 1) characterization of the risk triaging tools; 2) tool performance metrics (sensitivity, specificity, positive and negative predictive value, area under the curve); and 3) health system effects (efficiency, acceptability, resource utilization, cost). We report outcomes for each eligible study and identify lessons for use of risk triaging.

Results

Of 1,876 articles identified, 28 were eligible for our review. Thirteen addressed HIV, 10 TB, 1 TB/HIV, and 4 other conditions. Approximately 60% used existing, retrospective data to identify important risk factors for an outcome and then construct a scoring system, but no implementation of these tools was reported. The remaining 40% designed a tool using existing data or experience and reported implementation results. More than half (16/28, 58%) of the tools achieved sensitivities >80%; specificity was much lower. Only one tool, the World Health Organization’s 4-symptom screen for tuberculosis, had been scaled up widely. While most studies claimed that their tools could increase the efficiency of healthcare delivery, none of the studies provided examples of tangible health system impacts.

Conclusion

Most of the tools identified were at least somewhat successful in identifying potential risks but uptake by health systems has been minimal. Although well-designed risk triaging tools have the potential to improve health outcomes, implementation will require commitment at the policy, operational, and funding levels.
Intravenous Thrombolysis before Thrombectomy Improves Functional Outcome after Stroke Independent of Reperfusion Grade
Authors: Sedghi Annahita , Kaiser Daniel P. O. , Cuberi Ani , Schreckenbauer Sonja , Wojciechowski Claudia , Friehs Ingeborg , Reichmann Heinz , Barlinn Jessica , Barlinn Kristian , Puetz Volker , Siepmann Timo
Published: July 2023

Background

We studied the effect of bridging intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large vessel occlusion (acLVO) on functional outcome and scrutinized its dependence on grade of reperfusion and distal thrombus migration.

Methods

We included consecutive acLVO patients from our prospective registry of thrombectomy-eligible patients treated from 01/01/2017 to 01/01/2023 at a tertiary stroke center in Germany into a retrospective cohort study. We evaluated the effects of bridging IVT on functional outcome quantified via modified Rankin scale (mRS) at 90 days applying multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics, onset-to-recanalization time and distal thrombus migration. We performed sensitivity analysis using propensity score matching.

Results

In our study population of 1000 thrombectomy-eligible patients (513 females, median age 77 [67-84, interquartile range]) IVT emerged as predictor of favorable functional outcome (mRS 0-2) independent of mTICI (adjusted OR 0.49; 95% CI [0.32;0.75]; p=0.001). In those who underwent thrombectomy (n=812) the association of IVT and favorable functional outcome was reproduced (adjusted OR 0.49; 95% CI [0.31;0.74]; p=0.001) and was further confirmed on propensity score analysis where IVT led to a 0.35-point decrease in 90-day mRS score [ß=-0.35; 95CI% [-0.68;-0.01]; p=0.04]. The additive benefit of IVT remained independent of mTICI (ß=-1.79; 95% CI [-3.43;-0.15]; p=0.03) and distal thrombus migration (ß=-0.41; 95% CI [-0.69;-0.13]; p=0.004) on interaction analysis. Consequently, IVT showed an additive effect on functional outcome in the subpopulation of thrombectomy patients who achieved successful reperfusion (TICI≥2b; ß=-0.46; 95% CI [-0.74;-0.17]; p=0.002) and remained beneficial in those with unsuccessful reperfusion (TICI≤2a; ß=-0.47; 95% CI [-0.96;-0.01]; p=0.05).

Conclusions

In thrombectomy-eligible acLVO patients IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.
Epitope Engineered Human Haematopoietic Stem Cells are Shielded from CD123-targeted Immunotherapy
Authors: Marone Romina , Landmann Emmanuelle , Devaux Anna , Lepore Rosalba , Seyres Denis , Zuin Jessica , Burgold Thomas , Engdahl Corinne , Capoferri Giuseppina , Dell’Aglio Alessandro , Larrue Clément , Simonetta Federico , Rositzka Julia , Rhiel Manuel , Andrieux Geoffroy , Gallagher Danielle , Schröder Markus , Wiederkehr Amélie , Sinopoli Alessandro , Do Sacramento Valentin , Haydn Anna , Garcia-Prat Laura , Divsalar Christopher , Camus Anna , Xu Liwen , Bordoli Lorenza , Schwede Torsten , Porteus Matthew , Bonnefoy Jérôme Tamburini , Corn Jacob E. , Cathomen Toni , Cornu Tatjana I. , Urlinger Stefanie , Jeker Lukas T.
Published: July 2023

Targeted eradication of transformed or otherwise dysregulated cells using monoclonal antibodies (mAb), antibody-drug conjugates (ADC), T cell engagers (TCE) or chimeric antigen receptor (CAR) cells is very effective for haematologic diseases. Unlike the breakthrough progress achieved for B cell malignancies, there is a pressing need to find suitable antigens for immunotherapy of myeloid malignancies. CD123, the interleukin-3 (IL-3) receptor alpha-chain, is highly expressed in various haematological malignancies, including acute myeloid leukaemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). However, shared expression of CD123 on healthy haematopoietic stem and progenitor cells (HSPCs) bears the risk for extensive myelotoxicity upon targeted depletion. Here, we demonstrate that rationally designed, epitope-engineered HSPCs were completely shielded from CD123-targeted immunotherapy but remained fully functional while CD123-deficient HSPCs displayed a competitive disadvantage. Thus, molecularly shielded HSPCs could allow tumor-selective targeted immunotherapy and in parallel enable rebuilding a fully functional haematopoietic system. We envision that this approach is broadly applicable to many targets and cells, could render hitherto undruggable targets accessible to immunotherapy and will allow continued posttransplant immunotherapy, for instance to treat minimal residual disease (MRD) or be used as a salvage therapy. Since the function of the engineered targets is preserved, multiplexed molecular shielding could also enable targeted combination immunotherapies to address tumor heterogeneity. More generally, epitope shielding will be applicable for replacement of other cell types including the many immune cells which are currently being considered for engineered cellular therapies.
RNAGEN: A generative adversarial network-based model to generate synthetic RNA sequences to target proteins
Authors: Ozden Furkan , Barazandeh Sina , Akboga Dogus , Tabrizi Sobhan Shokoueian , Seker Urartu Ozgur Safak , Cicek A. Ercument
Published: July 2023

RNA - protein binding plays an important role in regulating protein activity by affecting localization and stability. While proteins are usually targeted via small molecules or other proteins, easy-to-design and synthesize small RNAs are a rather unexplored and promising venue. The problem is the lack of methods to generate RNA molecules that have the potential to bind to certain proteins. Here, we propose a method based on generative adversarial networks (GAN) that learn to generate short RNA sequences with natural RNA-like properties such as secondary structure and free energy. Using an optimization technique, we fine-tune these sequences to have them bind to a target protein. We use RNA-protein binding prediction models from the literature to guide the model. We show that even if there is no available guide model trained specifically for the target protein, we can use models trained for similar proteins, such as proteins from the same family, to successfully generate a binding RNA molecule to the target protein. Using this approach, we generated piRNAs that are tailored to bind to SOX2 protein using models trained for its relative (SOX10, SOX14, and SOX8) and experimentally validatedin vitrothat the top-2 molecules we generated specifically bind to SOX2.
Studies on the selectivity of the SARS-CoV-2 papain-like protease reveal the importance of the P2′ proline of the viral polyprotein
Authors: Chan H. T. Henry , Brewitz Lennart , Lukacik Petra , Strain-Damerell Claire , Walsh Martin A. , Schofield Christopher J. , Duarte Fernanda
Published: July 2023

The SARS-CoV-2 papain-like protease (PLpro) is an antiviral drug target that catalyzes the hydrolysis of the viral polyproteins pp1a/1ab, releasing the non-structural proteins (nsps) 1-3 that are essential for the coronavirus lifecycle. The LXGG↓X motif found in pp1a/1ab is crucial for recognition and cleavage by PLpro. We describe molecular dynamics, docking, and quantum mechanics/molecular mechanics (QM/MM) calculations to investigate how oligopeptide substrates derived from the viral polyprotein bind to PLpro. The results reveal how the substrate sequence affects the efficiency of PLpro-catalyzed hydrolysis. In particular, a proline at the P2′ position promotes catalysis, as validated by residue substitutions and mass spectrometry-based analyses. Analysis of PLprocatalyzed hydrolysis of LXGG motif-containing oligopeptides derived from human proteins suggests that factors beyond the LXGG motif and the presence of a proline residue at P2′ contribute to catalytic efficiency, possibly reflecting the promiscuity of PLpro. The results will help in identifying PLprosubstrates and guiding inhibitor design.
Blood pressure lowering enhances cerebrospinal fluid efflux primarily via the lymphatic vasculature
Authors: Jukkola Jari , Kaakinen Mika , Singh Abhishek , Moradi Sadegh , Ferdinando Hany , Myllylä Teemu , Kiviniemi Vesa , Eklund Lauri
Published: July 2023

Background

Inside the incompressible cranium, the volume of cerebrospinal fluid (CSF) is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering (BPL) on fluorescent CSF tracer absorption into the systemic blood circulation.

Methods

BPL was performed by an i.v. administration of nitric oxide donor sodium nitroprusside (5 µg kg-1min-1) or the Ca2+-channel blocker nicardipine hydrochloride (0.5 µg kg-1min-1) for 10 and 15 to 40 mins, respectively. The effect of BPL on CSF clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes.

Results

Nicardipine and sodium nitroprusside reduced blood pressure by 32.0 ± 19.6% and 22.0 ± 2.5%, while temporarily elevating in intracranial pressure by 14.0 ± 6.0% and 11.6 ± 2.0%, respectively. BPL significantly increased tracer accumulation into deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by BPL into the systemic circulation was markedly reduced (-66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes.

Conclusions

This is the first study showing that CSF clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced CSF clearance by BPL may have therapeutic potential in diseases with dysregulated CSF flow.
Ankyrin B Promotes Developmental Spine Regulation in the Mouse Prefrontal Cortex
Authors: Murphy Kelsey E. , Duncan Bryce W. , Sperringer Justin E. , Zhang Erin Y. , Haberman Victoria A. , Wyatt Elliott V. , Maness Patricia F.
Published: July 2023

Postnatal regulation of dendritic spine formation and refinement in cortical pyramidal neurons is critical for excitatory/inhibitory balance in neocortical networks. Recent studies have identified a selective spine pruning mechanism in the mouse prefrontal cortex (PFC) mediated by class 3 Semaphorins and the L1-CAM cell adhesion molecules Neuron-glia related CAM (NrCAM), Close Homolog of L1 (CHL1), and L1. L1-CAMs bind Ankyrin B (AnkB), an actin-spectrin adaptor encoded byAnkyrin2(ANK2), a high confidence gene for autism spectrum disorder (ASD). In a new inducible mouse model (Nex1Cre-ERT2:Ank2flox: RCE),Ank2deletion in early postnatal pyramidal neurons increased spine density on apical dendrites in PFC layer 2/3 of homozygous and heterozygousAnk2-deficient mice. In contrast,Ank2deletion in adulthood had no effect on spine density. Sema3F-induced spine pruning was impaired in cortical neuron cultures from AnkB-null mice and was rescued by re-expression of the 220 kDa AnkB isoform but not 440 kDa AnkB. AnkB bound to NrCAM at a cytoplasmic domain motif (FIGQY1231), and mutation to FIGQH inhibited binding, impairing Sema3F-induced spine pruning in neuronal cultures. Identification of a novel function for AnkB in dendritic spine regulation provides insight into cortical circuit development, as well as potential molecular deficiencies in ASD.
Time course of EEG complexity reflects attentional engagement during listening to speech in noise
Authors: Eqlimi Ehsan , Bockstael Annelies , Schönwiesner Marc , Talsma Durk , Botteldooren Dick
Published: July 2023

Distraction caused by auditory noise poses a considerable challenge to the quality of information encoding in speech comprehension. The aim of this study was to explore the temporal dynamics and complexity of electroencephalog-raphy (EEG) microstates in relation to attentional engage-ment over time, contributing to the understanding of speech perception in noise. We examined three listening condi-tions: speech perception with background noise, focused attention on the background noise, and intentional disre-gard of the background noise. Our findings revealed an increase in complexity during the transition of microstates and a slower microstate recurrence when individuals directed their attention to speech compared to tasks without speech. Additionally, a two-stage time course for both microstate complexity and alpha-to-theta power ratio was observed. Specifically, in the early epochs, a lower level was observed, which gradually increased and eventually reached a steady level in the later epochs. The findings suggest that the ini-tial stage is primarily driven by sensory processes and infor-mation gathering, while the second stage involves higher-level cognitive engagement, including mnemonic binding and memory encoding.
Enhanced long-term memory and increased mushroom body plasticity inHeliconiusbutterflies
Authors: Young Fletcher J. , Alcalde Amaia , Melo-Flórez Lina , Couto Antoine , Foley Jessica , Monllor Monica , McMillan W. Owen , Montgomery Stephen H.
Published: July 2023

As highly labile structures on both individual and evolutionary time-scales, the mushroom bodies, a key site of learning and memory in insects, are an excellent model for investigating the evolution of cognitive variation. We explored the behavioural consequences of mushroom body expansion inHeliconiusbutterflies, which possess greatly expanded mushroom bodies relative to their closest outgroups. We conducted long-term visual memory assays across threeHeliconiusand three other Heliconiini species using trained food-colour associations. We confirm robust differences between clades, withHeliconiusexhibiting greater fidelity to the trained colour after 8 days without reinforcement compared to other Heliconiini, with further evidence of stable preferences at 13 days. We extended this analysis to consider the plastic response of the mushroom body calyces over this time period, measuring the volume of the mushroom body calyx, and the number of neurons and synapses it contains. We find substantial post-eclosion expansion and synaptic pruning in calyx ofHeliconius erato, but not inDryas iulia. InHeliconius erato, visual associative learning experience specifically is associated with a greater retention of calyceal synapses. At an individual level, fidelity to the trained colour inHeliconius eratowas also positively correlated with synapse number. These results point to an enhanced visual long-term memory acrossHeliconius, facilitated not only by phylogenetic expansion of the mushroom body, but also changes in its developmental response to learning experience. The co-evolution of mushroom body expansion, plasticity and specific behaviours provides an important case study in the evolution of cognition.

Significance Statement

How are cognitive differences between species supported by evolutionary changes in the brain? We investigated this question usingHeliconiusbutterflies which have expanded mushroom bodies, a region of the insect brain involved in learning and memory. We show thatHeliconiushave more stable visual long-term memories and exhibit more substantial age- and experience-related plasticity than a closely related genus with smaller mushroom bodies. Recall accuracy was also predicted by synapse number inHeliconius erato, but notDryas iulia, suggesting functional importance. These results suggest that increases in the size of specific brain regions and changes in their plastic response to experience may co-evolve to shape the evolution of cognition.
Spatial reorganization ofEscherichia colichromosome contextualizes triclosan stress-related genetic, epigenetic and transcriptome changes
Authors: Ghosh Dipannita , Evans Benjamin A. , Vivekanandan Perumal
Published: July 2023

Changes in the spatial organization of bacterial chromosomes under stress conditions and its biological implications remain poorly understood. We mapped the structural landscape of wild-type and Δdcm E. colichromosomes under triclosan stress using Hi-C to identify triclosan-induced chromosomal interaction domains (CIDs). Two CIDs were common to the wild-type and Δdcm E. coli, including a CID with a common boundary atfabIgene, which encodes the triclosan target. All mutations and structural variants under triclosan stress were observed within or in close proximity to triclosan-induced CIDs. Absence of Dcm methylation impacts both short- and long-range interactions in triclosan stress. Single-base resolution methylome maps reveal hypermethylation of adenines (in wild-type and Δdcm) and cytosines (in wild-type) in the two common triclosan-induced CIDs. Furthermore, global gene expression profiling identified enrichment of highly expressed genes within the two common CIDs. Our findings suggest that stress-induced CIDs inE. coliare hotspots for genetic variations and are associated with enhanced transcriptional activity and hypermethylation of Dam/Dcm motifs.
Urbanization spreads antimicrobial resistant enteric pathogens in wild bird microbiomes
Authors: Mourkas Evangelos , Valdebenito José O. , Marsh Hannah , Hitchings Matthew D. , Cooper Kerry K. , Parker Craig T. , Székely Tamás , Johansson Håkan , Ellström Patrik , Pascoe Ben , Waldenström Jonas , Sheppard Samuel K.
Published: July 2023

Human behaviour is dramatically changing global ecology. Nowhere is this more apparent than in urbanization, where novel high human density habitats are disrupting long established ecotones. Resultant changes to the transitional areas between organisms, especially enhanced contact between humans and wild animals, provides new opportunities for the spread of zoonotic pathogens, posing a serious threat to global public health. Here, by studying the multi-host enteric pathogenCampylobacter jejuniisolated from the gut of 30 bird species in 8 countries, we investigated how proximity to urbanization influenced the spread of antimicrobial resistant (AMR) strains. Generalized linear models compared multiple behavioural and ecological traits and confirmed a positive correlation between proximity to urbanization and the number ofC. jejunigenotypes and AMR genes in wild bird hosts. Wild birds from highly urban areas harboured up to four times moreC. jejunigenotypes and six times more AMR genes. This is consistent with increased frequency of transition events. Quantifying zoonotic transmission and gene pool spread is essential for quantitative one health surveillance and control measures against future zoonosis emergences.
The Landscape of Maize-Associated Bacteria and Fungi Across the United States
Authors: Schultz Corey R , Desai Hanish , Wallace Jason G
Published: July 2023

The maize microbiome consists of microbes that are associated with plants, and can be shaped by the host plant, the environment, and microbial partners, some of which can impact plant performance. We used a public dataset to analyze bacteria and fungi in the soil, rhizosphere, roots, and leaves of commercial maize at 30 locations across the US. We found that both tissue type and location had significant effects on community structure and makeup, although the patterns differed in bacteria and fungi based on tissue type. We also found many differences in predicted microbial gene pathways between tissues, with location also shaping predicted functional gene profiles. We found a pattern of potential interaction between fungi and bacteria, and potential intra-kingdom mutualism, in microbiome networks. The robustness of these networks was dependent upon tissue, with endophytes in leaves and roots showing significantly higher natural connectivity. Within a tissue, this connectivity was relatively stable across locations. We identified environment and soil characteristics that may impact tissue specific microbial abundance. Sulfate level in the soil was positively correlated with Proteobacteria abundance, but negatively correlated with Firmicutes abundance in the roots and leafs. Ascomycota appears to be affected by different environmental variables in each tissue. We also identified gene functions and enzymes which may be necessary to allow microbes to transition across compartments and become endophytes.
Spontaneous biases enhance generalisation in the neonate brain
Authors: Wang Shuge , Vasas Vera , Freeland Laura , Osorio Daniel , Versace Elisabetta
Published: July 2023

The ability to use sparse evidence to produce adaptive responses in new contexts and to new stimuli (inductive generalisation) is central to biological and artificial intelligence. Young and inexperienced animals require very little evidence to generalise, raising the question of whether the neonate brain is evolutionarily prepared (predisposed) for generalisation. To understand the principles of spontaneous generalisation, we exposed neonate chicks to an artificial social partner of a specific colour, and measured generalisation by comparing responses to novel and familiar stimuli along either the red-yellow or the blue-green colour continuum. Generalisation responses were inconsistent with an unbiased model, showing biases such as asymmetrical generalisation gradients, faster learning for particular colours (red and blue over yellow and green), preferences for unfamiliar stimuli and different time courses in learning. Moreover, the chicks’ generalisation behaviour was consistent with a Bayesian theoretical model that explicitly incorporates predispositions as initial preferences and treats the learning process as an update of spontaneous preferences. These results show that neonate animals are evolutionarily prepared for generalisation, via biases that do not depend on experience, reinforcement or supervision. Biases that facilitate generalisation are tuned to distinctive features that are unusual in the natural environment, such as the red and blue colours. Predispositions facilitate or hinder learning in the inexperienced brain, determining how experience is used to update the likelihood of predictive models. Neonate animals use spontaneous biases to solve the problem of induction.
The bigger picture: global analysis of solubilization performance of classical detergents versus new synthetic polymers utilizing shotgun proteomics
Authors: Mueller Stefan , Kubicek Jan , Merino Felipe , Hanisch Philipp , Maertens Barbara , Lackmann Jan-Wilm
Published: July 2023

Integral membrane proteins are critical for many cellular functions. Roughly 25% of all human genes code for membrane proteins, and about 70% of all approved drugs target them. Despite their importance, laborious and harsh purification conditions often hinder their characterization. Traditionally, they are removed from the membrane using detergents, thereby taking the proteins out of their native environment, affecting their function. Recently, a variety of synthetic polymers have been introduced, which can extract membrane proteins together with their native lipids into a so-called native nanodisc. However, they usually show lesser solubilization capacity than detergents, and their general applicability for membrane protein biochemistry is poorly understood. Here, we used Hek293 cell membrane extracts and LC-MS-based proteomics to compare the ability of nanodisc-forming polymers against state-of-the- art detergents to solubilize the membrane proteome. Our data demonstrates the general ability of synthetic co-polymers to extract membrane proteins, rivaling the efficacy of commonly used detergents. Interestingly, each class of solubilization agent presents specific solubilization profiles. We found no correlation between efficiency and number of transmembrane domains, isoelectric point, or GRAVY score for any compound. Our data shows that these polymers are a versatile alternative to detergents for the biochemical and structural study of membrane proteins, functional proteomics, or as components of native lysis/solubilization buffers. Our work here represents the first attempt at a proteome-scale comparison of the efficacy of nanodisc-forming polymers. These data should serve as starting reference for researchers looking to purify membrane proteins in near native conditions.
Beyond the Visual Word Form Area: Characterizing a hierarchical, distributed and bilateral network for visual word processing
Authors: Vin Raina , Blauch Nicholas M. , Plaut David C. , Behrmann Marlene
Published: July 2023

Although the left hemisphere (LH) Visual Word Form Area (VWFA) is considered the pre-eminent cortical region engaged in visual text processing, other regions in both hemispheres have also been implicated. To examine the entire circuit, using functional MRI data, we defined ten regions of interest (ROI) in each hemisphere that, based on functional connectivity measures, naturally grouped into early vision, high-level vision, and language clusters. We analysed univariate and multivariate responses to words, inverted words, and consonant strings for ROIs and clusters, and demonstrated modulation by text condition bihemispherically, albeit more strongly and in a larger number of regions in the LH. Graph theory analysis revealed that the high-level vision cluster and, specifically, the VWFA was equivalently connected with both early visual and language clusters in both hemispheres, reflecting its role as a mediator in the circuit. Our findings reveal bihemispheric, stimulus-mediated ROI response flexibility but circuit-level connectivity stability, reflecting the complex contribution of a distributed system for word processing.
GIGANTEAaccelerates wheat heading time through gene interactions converging onFLOWERING LOCUS T1
Authors: Li Chengxia , Lin Huiqiong , Debernardi Juan M. , Zhang Chaozhong , Dubcovsky Jorge
Published: July 2023

Precise regulation of flowering time is critical for cereal crops to synchronize reproductive development with optimum environmental conditions, thereby maximizing grain yield. The plant specific geneGIGANTEA(GI) plays an important role in the control of flowering time, with additional functions on the circadian clock and plant stress responses. In this study, we show thatGIloss-of-function mutants in a photoperiod sensitive tetraploid wheat background exhibit significant delays in heading time under both long-day (LD) and short-day (SD) photoperiods, with stronger effects under LD. However, this interaction between GI and photoperiod is no longer observed in isogenic lines carrying either a photoperiod insensitive allele in thePHOTOPERIOD1(PPD1) gene or a loss-of-function allele inEARLY FLOWERING 3(ELF3), a known repressor ofPPD1.These results suggest that the normal circadian regulation ofPPD1is required for the differential effect ofGIon heading time in different photoperiods. Using crosses between mutants or transgenic ofGIand those of critical genes in the flowering regulation pathway, we show thatGIaccelerates wheat heading time by promotingFLOWERING LOCUS T1(FT1) expression via interactions withELF3, VERNALIZATION 2(VRN2),CONSTANS(CO), and the age-dependent microRNA172-APETALA2(AP2) pathway, at both transcriptional and protein levels. Our study reveals conservedGImechanisms between wheat and Arabidopsis, but also identifies specific interactions of GI with the distinctive photoperiod and vernalization pathways of the temperate grasses. These results provide valuable knowledge for modulating wheat heading time and engineering new varieties better adapted to a changing environment.
Distinct neural signatures underlying information manipulation in working memory
Authors: Shi Dongping , Yu Qing
Published: July 2023

Working memory is a core cognitive ability that supports both the maintenance and manipulation of information in mind to serve complex behavior. Previously, stimulus representation in memory maintenance has been observed in both voltage and alpha-band activity in electroencephalography (EEG). However, the exact function of these two neural signatures in working memory has remained elusive. Here we systematically examined this question by asking whether memory manipulation is supported by the same neural signatures as memory maintenance. Human participants either maintained a previously-seen spatial location, or manipulated the spatial location according to a mental rotation cue over a delay. Using multivariate distance-based decoding, we observed robust neural representations of maintained and manipulated locations in both low-frequency voltage and alpha-band oscillatory activity, suggesting that memory maintenance and manipulation are supported by multiple overlapping neural signatures in EEG. Yet, these neural signatures demonstrated distinct spatiotemporal dynamics: location representations in alpha-band activity were most evident in the posterior channels, while location representations in voltage were most evident in the more anterior, central channels. The temporal emergence of manipulated representation in central voltage also preceded that in posterior alpha-band activity, suggesting that voltage might carry stimulus-specific source signals originated internally from more anterior cortex, whereas alpha-band activity might reflect feedback signals in posterior cortex received from higher-order cortex. Lastly, while location representations in both signals could be compressed into a low-dimensional neural subspace, location representation in central voltage was higher-dimensional and underwent a representational transformation that exclusively predicted memory behavior. Together, these results highlight the crucial role of central voltage in memory manipulation, as well as offer direct experimental evidence supporting functional distinction between voltage and alpha-band oscillatory activity in EEG.
AI in Medical Education: A Comparative Analysis of GPT-4 and GPT-3.5 on Turkish Medical Specialization Exam Performance
Authors: Kılıç Mustafa Eray
Published: July 2023

Background/aim

Large-scale language models (LLMs), such as GPT-4 and GPT-3.5, have demonstrated remarkable potential in the rapidly developing field of artificial intelligence (AI) in education. The use of these models in medical education, especially their effectiveness in situations such as the Turkish Medical Specialty Examination (TUS), is yet understudied. This study evaluates how well GPT-4 and GPT-3.5 respond to TUS questions, providing important insight into the real-world uses and difficulties of AI in medical education.

Materials and methods

In the study, 1440 medical questions were examined using data from six Turkish Medical Specialties examinations. GPT-4 and GPT-3.5 AI models were utilized to provide answers, and IBM SPSS 26.0 software was used for data analysis. For advanced enquiries, correlation analysis and regression analysis were used.

Results

GPT-4 demonstrated a better overall success rate (70.56%) than GPT-3.5 (40.17%) and physicians (38.14%) in this study examining the competency of GPT-4 and GPT-3.5 in answering questions from the Turkish Medical Specialization Exam (TUS). Notably, GPT-4 delivered more accurate answers and made fewer errors than GPT-3.5, yet the two models skipped about the same number of questions. Compared to physicians, GPT-4 produced more accurate answers and a better overall score. In terms of the number of accurate responses, GPT-3.5 performed slightly better than physicians. Between GPT-4 and GPT-3.5, GPT-4 and the doctors, and GPT-3.5 and the doctors, the success rates varied dramatically. Performance ratios differed across domains, with doctors outperforming AI in tests involving anatomy, whereas AI models performed best in tests involving pharmacology.

Conclusions

In this study, GPT-4 and GPT-3.5 AI models showed superior performance in answering Turkish Medical Specialization Exam questions. Despite their abilities, these models demonstrated limitations in reasoning beyond given knowledge, particularly in anatomy. The study recommends adding AI support to medical education to enhance the critical interaction with these technologies.
The role and influence of perceived experts in an anti-vaccine misinformation community
Authors: Harris Mallory J. , Murtfeldt Ryan , Wang Shufan , Mordecai Erin A. , West Jevin D.
Published: July 2023

1

The role of perceived experts (i.e., medical professionals and biomedical scientists) as potential anti-vaccine influencers has not been characterized systematically. We describe the prevalence and importance of anti-vaccine perceived experts by constructing a coengagement network based on a Twitter data set containing over 4.2 million posts from April 2021. The coengagement network primarily broke into two large communities that differed in their stance toward COVID-19 vaccines, and misinformation was predominantly shared by the anti-vaccine community. Perceived experts had a sizable presence within the anti-vaccine community and shared academic sources at higher rates compared to others in that community. Perceived experts occupied important network positions as central anti-vaccine nodes and bridges between the anti- and pro-vaccine communities. Perceived experts received significantly more engagements than other individuals within the anti- and pro-vaccine communities and there was no significant difference in the influence boost for perceived experts between the two communities. Interventions designed to reduce the impact of perceived experts who spread anti-vaccine misinformation may be warranted.
A Population Level Study on the Determinants of COVID-19 Vaccine Hesitancy at the U.S. County Level
Authors: Dong Ensheng , Nixon Kristen , Gardner Lauren M.
Published: July 2023

Multiple COVID-19 vaccines were proven to be safe and effective in curbing severe illness, but despite vaccine availability, uptake rates were relatively low in the United States (U.S.), primarily due to vaccine hesitancy. To better understand factors associated with COVID-19 vaccine hesitancy in the U.S., our study provides a comprehensive, data-driven population-level statistical analysis at the county level. We find that political affiliation, as determined by the proportion of votes received by the Republican candidate in the 2020 presidential election, has the strongest association with COVID-19 vaccine hesitancy. The next strongest association was median household income, which has a negative association. The percentage of Black people and the average number of vehicles per household are also positively associated with vaccine hesitancy. In contrast, COVID-19 infection rate, percentage of Hispanic people, postsecondary education percentage, median age, and prior non-COVID-19 childhood vaccination coverage are other factors negatively associated with vaccine hesitancy. Unlike previous studies, we do not find significant relationships between cable TV news viewership or Twitter misinformation variables with COVID-19 vaccine hesitancy. These results shed light on some factors that may impact vaccination choice in the U.S. and can be used to target specific populations for educational outreach and vaccine campaign strategies in efforts to reduce vaccine hesitancy.
Pharmacological characterization and radiolabeling of VUF15485, a high-affinity small-molecule agonist for the atypical chemokine receptor ACKR3
Authors: Zarca Aurelien M. , Adlere Ilze , Viciano Cristina P. , Arimont-Segura Marta , Meyrath Max , Simon Icaro A. , Bebelman Jan Paul , Laan Dennis , Custers Hans G. J. , Janssen Elwin , Versteegh Kobus L. , Bosma Reggie , de Esch Iwan J. P. , Vischer Henry F. , Wijtmans Maikel , Szpakowska Martyna , Chevigné Andy , Hoffmann Carsten , de Graaf Chris , Zarzycka Barbara A. , Windhorst Albert D. , Smit Martine J. , Leurs Rob
Published: July 2023

Atypical chemokine receptor 3 (ACKR3), formerly referred to as CXCR7, is considered to be an interesting drug target. In this study we report on the synthesis, pharmacological characterization and radiolabeling of VUF15485, a new ACKR3 small-molecule agonist, that will serve as an important new tool to study this β-arrestin-biased chemokine receptor. VUF15485 binds with nanomolar affinity (pIC50= 8.3) to human ACKR3, as measured in [125I]CXCL12 competition binding experiments. Moreover, in a BRET-based β-arrestin2 recruitment assay VUF15485 acts as an ACKR3 agonist with high potency (pEC50= 7.6) and shows a similar extent of receptor activation compared to CXCL12 when using a newly developed, FRET-based ACKR3 conformational sensor. Moreover, the ACKR3 agonist VUF15485 was tested against a (atypical) chemokine receptor panel (agonist and antagonist mode) and proves to be selective for ACKR3. VUF15485 was subsequently labeled with tritium at one of its methoxy groups affording [3H]VUF15485. The small-molecule agonist radioligand binds saturably and with high affinity to human ACKR3 (Kd= 8.2 nM). [3H]VUF15485 shows rapid binding kinetics and consequently a short residence time (RT < 2 min) for its binding to ACKR3. Displacement of [3H]VUF15485 binding to membranes of HEK293T cells, transiently expressing ACKR3, with a number of CXCR3, CXCR4 or ACKR3 small-molecule ligands confirmed the ACKR3 profile of the [3H]VUF15485 binding site. Interestingly, the chemokine ligands CXCL11 and CXCL12 are not able to displace the binding of [3H]VUF15485 to ACKR3. The radiolabeled VUF15485 was subsequently used to evaluate its binding pocket. Site-directed mutagenesis and docking studies using a recently solved cryo-EM structure propose VUF15485 to bind in the major and the minor binding pocket of ACKR3.
Genome sequencing of Syzygium cumini (Jamun) reveals adaptive evolution in secondary metabolism pathways associated with its medicinal properties
Authors: Chakraborty Abhisek , Mahajan Shruti , Bisht Manohar S. , Sharma Vineet K.
Published: July 2023

Syzygium cumini, also known as jambolan or jamun, is an evergreen tree widely known for its medicinal properties, fruits, and ornamental value. To understand the genomic and evolutionary basis of its medicinal properties, we sequenced S. cumini genome, which is the largest genome sequenced for the first time from the world’s largest tree genus Syzygium using Oxford Nanopore and 10x Genomics sequencing technologies. The tetraploid and highly heterozygous draft genome of S. cumini had a total size of 709.9 Mbp with 61,195 coding genes. The phylogenetic position of S. cumini was established using a comprehensive genome-wide analysis including species from 18 Eudicot plant orders. The existence of neopolyploidy in S. cumini was evident from the higher number of coding genes and expanded gene families compared to the other two sequenced species from this genus. Comparative evolutionary analyses showed the adaptive evolution of genes involved in the phenylpropanoid-flavonoid (PF) biosynthesis pathway and other secondary metabolites biosynthesis such as terpenoid and alkaloid in S. cumini, along with genes involved in stress tolerance mechanisms, which was also supported by leaf transcriptome data generated in this study. The adaptive evolution of secondary metabolism pathways is associated with the wide range of pharmacological properties, specifically the anti-diabetic property, of this species conferred by the bioactive compounds that act as nutraceutical agents in modern medicine.
Polarized localization of kinesin-1 and RIC-7 drives axonal mitochondria anterograde transport
Authors: Wu Youjun , Ding Chen , Weinreb Alexis , Manning Laura , Swaim Grace , Yogev Shaul , Colón-Ramos Daniel A. , Hammarlund Marc
Published: July 2023

Mitochondria transport is crucial for mitochondria distribution in axons and is mediated by kinesin-1-based anterograde and dynein-based retrograde motor complexes. While Miro and Milton/TRAK were identified as key adaptors between mitochondria and kinesin-1, recent studies suggest the presence of additional mechanisms. InC. elegans,ric-7is the only single gene described so far, other than kinesin-1, that is absolutely required for axonal mitochondria localization. Using CRISPR engineering inC. elegans, we find that Miro is important but is not essential for anterograde traffic, whereas it is required for retrograde traffic. Both the endogenous RIC-7 and kinesin-1 act at the leading end to transport mitochondria anterogradely. RIC-7 recruitment to mitochondria requires its N-terminal domain and partially relies on MIRO-1, whereas RIC-7 accumulation at the leading end depends on its disordered region, kinesin-1 and metaxin2. We conclude that polarized transport complexes containing kinesin-1 and RIC-7 form at the leading edge of mitochondria, and that these complexes are required for anterograde axonal transport.

Summary statement

Anterograde transport of axonal mitochondria is critical for maintenance of the mitochondria pool and neuronal health. Wu et al. show that the endogenous kinesin-1 and RIC-7 localize at the leading end of mitochondria to drive axonal anterograde transportin vivo.