bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concepts as plug & play devices
Authors: Shea Nicholas 
Published: December 2022

Research on concepts has focused on categorization. Categorization starts with a stimulus. Equally important are episodes that start with a thought. We engage in thinking to draw out new consequences from stored information, or to work out how to act. Each of the concepts out of which thought is constructed provides access to a large body of stored information. Access is not always just a matter of retrieving a stored belief (semantic memory). Often it depends on running a simulation. Simulation allows conceptual thought to draw on information in special-purpose systems, information stored in special-purpose computational dispositions and special-purpose representational structures. While the utility of simulation, prospection or imagination is widely appreciated, the role of concepts in the process is not well understood. This paper turns to cognitive and computational neuroscience for a model of how simulations enable thinkers to reach novel conclusions. Carried over to conceptual thought, the model suggests that concepts are ‘plug & play’ devices. The distinctive power of thought-driven simulation derives from the ability of concepts to plug into two kinds of structure at once: the combinatorial structure of a thought at one end and special-purpose structural representations at the other.
This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
Is love an abstract concept? A view of concepts from an interaction-based perspective
Authors: Rączaszek-Leonardi Joanna , Zubek Julian 
Published: December 2022

Research concerning concepts in the cognitive sciences has been dominated by the information-processing approach, which has resulted in a certain narrowing of the range of questions and methods of investigation. Recent trends have sought to broaden the scope of such research, but they have not yet been integrated within a theoretical framework that would allow us to reconcile new perspectives with the insights already obtained. In this paper, we focus on the processes involved in early concept acquisition and demonstrate that certain aspects of these processes remain largely understudied. These aspects include the primacy of movement and coordination with others within a structured social environment as well as the importance of first-person experiences pertaining to perception and action. We argue that alternative approaches to cognition, such as ecological psychology, enactivism and interactivism, are helpful for foregrounding these understudied areas. These approaches can complement the extant research concerning concepts to help us obtain a more comprehensive view of knowledge structures, thus providing us with a new perspective on recurring problems, suggesting novel questions and enriching our methodological toolbox.
This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
Mechanisms of alignment: shared control, social cognition and metacognition
Authors: Gandolfi Greta , Pickering Martin J. , Garrod Simon 
Published: December 2022

In dialogue, speakers process a great deal of information, take and give the floor to each other, and plan and adjust their contributions on the fly. Despite the level of coordination and control that it requires, dialogue is the easiest way speakers possess to come to similar conceptualizations of the world. In this paper, we show how speakers align with each other by mutually controlling the flow of the dialogue and constantly monitoring their own and their interlocutors' way of representing information. Through examples of conversation, we introduce the notions of shared control, meta-representations of alignment and commentaries on alignment, and show how they support mutual understanding and the collaborative creation of abstract concepts. Indeed, whereas speakers can share similar representations of concrete concepts just by mutually attending to a tangible referent or by recalling it, they are likely to need more negotiation and mutual monitoring to build similar representations of abstract concepts.
This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
Social semantics: the organization and grounding of abstract concepts
Authors: Pexman Penny M. , Diveica Veronica , Binney Richard J. 
Published: December 2022

Abstract concepts, likejusticeandfriendship, are central features of our daily lives. Traditionally, abstract concepts are distinguished from other concepts in that they cannot be directly experienced through the senses. As such, they pose a challenge for strongly embodied models of semantic representation that assume a central role for sensorimotor information. There is growing recognition, however, that it is possible for meaning to be ‘grounded’ via cognitive systems, including those involved in processing language and emotion. In this article, we focus on the specific proposal thatsocialsignificance is a key feature in the representation of some concepts. We begin by reviewing recent evidence in favour of this proposal from the fields of psycholinguistics and neuroimaging. We then discuss the limited extent to which there is consensus about the definition of ‘socialness’ and propose essential next steps for research in this domain. Taking one such step, we describe preliminary data from an unprecedented large-scale rating study that can help determine how socialness is distinct from other facets of word meaning. We provide a backdrop of contemporary theories regarding semantic representation and social cognition and highlight important predictions for both brain and behaviour.This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
Social concepts and the cerebellum: behavioural and functional connectivity signatures in cerebellar ataxic patients
Authors: Lopes da Cunha Pamela , Fittipaldi Sol , González Campo Cecilia , Kauffman Marcelo , Rodríguez-Quiroga Sergio , Yacovino Darío Andrés , Ibáñez Agustín , Birba Agustina , García Adolfo M. 
Published: December 2022

Neurocognitive research on social concepts underscores their reliance on fronto-temporo-limbic regions mediating broad socio-cognitive skills. Yet, the field has neglected another structure increasingly implicated in social cognition: the cerebellum. The present exploratory study examines this link combining a novel naturalistic text paradigm, a relevant atrophy model and functional magnetic resonance imaging. Fifteen cerebellar ataxia (CA) patients with focal cerebellar atrophy and 29 matched controls listened to a social text (highlighting interpersonal events) as well as a non-social text (focused on a single person's actions), and answered comprehension questionnaires. We compared behavioural outcomes between groups and examined their association with cerebellar connectivity. CA patients showed deficits in social text comprehension and normal scores in the non-social text. Also, social text outcomes in controls selectively correlated with connectivity between the cerebellum and key regions subserving multi-modal semantics and social cognition, including the superior and medial temporal gyri, the temporal pole and the insula. Conversely, brain-behaviour associations involving the cerebellum were abolished in the patients. Thus, cerebellar structures and connections seem involved in processing social concepts evoked by naturalistic discourse. Such findings invite new theoretical and translational developments integrating social neuroscience with embodied semantics.
This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
Mapping the mental space of emotional concepts through kinematic measures of decision uncertainty
Authors: Barca Laura , Candidi Matteo , Lancia Gian Luca , Maglianella Valerio , Pezzulo Giovanni 
Published: December 2022

Emotional concepts and their mental representations have been extensively studied. Yet, some ecologically relevant aspects, such as how they are processed in ambiguous contexts (e.g., in relation to other emotional stimuli that share similar characteristics), are incompletely known. We employed a similarity judgement of emotional concepts and manipulated the contextual congruency of the responses along the two main affective dimensions of hedonic valence and physiological activation, respectively. Behavioural and kinematics (mouse-tracking) measures were combined to gather a novel ‘similarity index’ between emotional concepts, to derive topographical maps of their mental representations. Self-report (interoceptive sensibility, positive–negative affectivity, depression) and physiological measures (heart rate variability, HRV) have been collected to explore their possible association with emotional conceptual representation. Results indicate that emotional concepts typically associated with low arousal profit by contextual congruency, with faster responses and reduced uncertainty when contextual ambiguity decreases. The emotional maps recreate two almost orthogonal axes of valence and arousal, and the similarity measure captures the smooth boundaries between emotions. The emotional map of a subgroup of individuals with low positive affectivity reveals a narrower conceptual distribution, with variations in positive emotions and in individuals with reduced arousal (such as those with reduced HRV). Our work introduces a novel methodology to study emotional conceptual representations, bringing the behavioural dynamics of decision-making processes and choice uncertainty into the affective domain.
This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
Abstract concepts and emotion: cross-linguistic evidence and arguments against affective embodiment
Authors: Winter Bodo 
Published: December 2022

How are abstract concepts such as ‘freedom' and ‘democracy' represented in the mind? One prominent proposal suggests that abstract concepts are grounded in emotion. Supporting this ‘affective embodiment' account, abstract concepts are rated to be more strongly positive or more strongly negative than concrete concepts. This paper demonstrates that this finding generalizes across languages by synthesizing rating data from Cantonese, Mandarin Chinese, Croatian, Dutch, French, German, Indonesian, Italian, Polish and Spanish. However, a deeper look at the same data suggests that the idea of emotional grounding only characterizes a small subset of abstract concepts. Moreover, when the concreteness/abstractness dimension is not operationalized using concreteness ratings, it is actually found that concrete concepts are rated as more emotional than abstract ones. Altogether, these results suggest limitations to the idea that emotion is an important factor in the grounding of abstract concepts.This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
Olfactory abstraction: a communicative and metacognitive account
Authors: Deroy Ophelia 
Published: December 2022

The usual puzzle raised about olfaction is that of a deficit of abstraction: smells, by contrast notably with colours, do not easily lend themselves to abstract categories and labels. Some studies have argued that the puzzle is culturally restricted and that abstraction is more common outside urban Western societies. Here, I argue that the puzzle is misconstrued and should be reversed: given that odours are constantly changing and that their commonalities are difficult for humans to identify, what is surprising is not that abstract terms are rare, but that they should be used at all for olfaction. Given the nature of the olfactory environment and our cognitive equipment, concrete labels referring to sources seem most adaptive. To explain the use and presence of abstract terms, we need to examine their social and communicative benefits. Here these benefits are spelt out as securing a higher agreement among individuals varying in their olfactory experiences as well as the labels they use, as well as feeling a heightened sense of confidence in one's naming capacities.
This article is part of the theme issue ‘Concepts in interaction: social engagement and inner experiences’.
First-in-human case report: AAV9-hGAA gene therapy for a patient with infantile-onset Pompe disease
Authors: Ma Xiuwei , Li Jun , Wang Xiaodong , Ma Wenhao , Wang Jianhua , Gu Ruijie , Zhu Zhiming , Wang Yongxia , Du Ying , Xu Juan , He Fang , Yang Xiao , Zhang Sheng , Zhu Lina , Li Qiuping , Xiong Hui , Wu Xiaobing , Feng Zhichun 
Published: December 2022

AbstractBackgroundThe classic infantile-onset Pompe disease (IOPD) is characterized by cardiac hypertrophy, respiratory insufficiency, and rapidly progressive muscle weakness due to the acid alpha-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) is the current approach for IOPD, but it entails several limitations. Aiming to overcome the limited efficiency of ERT, we developed adeno-associated virus (AAV) gene therapy for IOPD patients.MethodOne IOPD patient received a single intravenous dose of GC301, a recombinant adeno-associated virus 9 (rAAV9) expressing the human GAA (rAAV-hGAA). During the follow-up, safety was accessed by the physical examinations, cardiac and laboratory evaluations. GAA activity, the titers of serum antibodies to AAV9 and GAA, and motor development were monitored regularly.ResultThe infant showed significant improvements in motor milestones. The GAA enzyme activity increased to the normal range. The cardiac function improved notably.ConclusionIn patient with IOPD, a single intravenous AAV9-hGAA gene therapy improved the clinical outcomes remarkably. The trial is still ongoing, the safety of this gene therapy and the long-term clinical benefit remain to be monitored for months and years to come.
Genotype-driven downregulation of interleukin 6 signaling and periodontitis
Authors: Nolde Michael , Alayash Zoheir , Reckelkamm Stefan Lars , Kocher Thomas , Ehmke Benjamin , Holtfreter Birte , Baurecht Hansjörg , Georgakis Marios K. , Baumeister Sebastian-Edgar 
Published: December 2022

AbstractInterleukin 6 (IL-6) is considered to play a role in the dysbiotic host response in the development of periodontitis. To explore whether downregulation of IL-6 signaling could represent a viable treatment target for periodontitis, we tested the association of genetically proxied downregulation of IL-6 signaling with periodontitis. As proxies for IL-6 signaling downregulation, we selected 52 genetic variants in close vicinity of the gene encoding IL6 receptor (IL6R) that were associated with lower circulating C-reactive protein (CRP) levels in a genome-wide association study (GWAS) of 575,531 participants of European ancestry from the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Associations with periodontitis were tested with inverse-variance weighted Mendelian randomization in a study of 17,353 cases and 28,210 controls of European descent in the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) consortium. In addition, the effect of CRP reduction independent of the IL-6 pathway was assessed. Genetically proxied downregulation of IL-6 signaling was associated with lower odds of periodontitis (odds ratio (OR) = 0.81 per 1-unit decrement in log-CRP levels; 95% confidence interval (CI): [0.66;0.99]; P = 0.0497). Genetically proxied reduction of CRP independent of the IL-6 pathway had a similar effect (OR = 0.81; 95% CI: [0.68; 0.98]; P = 0.0296). In conclusion, genetically proxied downregulation of IL-6 signaling was associated with lower odds of periodontitis and CRP might be a causal target for the effect of IL-6 on the risk of periodontitis.
TaME-seq2: Tagmentation-assisted multiplex PCR enrichment sequencing for viral genomic profiling
Authors: Løvestad Alexander Hesselberg , Stosic Milan S. , Costanzi Jean-Marc , Christiansen Irene Kraus , Aamot Hege Vangstein , Ambur Ole Herman , Rounge Trine B. 
Published: December 2022

SummaryBackgroundPreviously developed TaME-seq method for deep sequencing of HPV, allowed simultaneous identification of the HPV DNA consensus sequence, low-frequency variable sites, and chromosomal integration events. The method has been successfully validated and applied to the study of five carcinogenic high-risk (HR) HPV types (HPV16, 18, 31, 33, and 45). Here, we present TaME-seq2 with an updated laboratory workflow and bioinformatics pipeline. The HR-HPV type repertoire was expanded with HPV51, 52, and 59. As a proof-of-concept, TaME-seq2 was applied on SARS-CoV-2 positive samples showing the method’s flexibility to a broader range of viruses, both DNA and RNA.ResultsCompared to TaME-seq version 1, the bioinformatics pipeline of TaME-seq2 is approximately 40x faster. In total, 23 HPV-positive samples and seven SARS-CoV-2 clinical samples passed the threshold of 300x mean depth and were submitted to further analysis. The mean number of variable sites per 1000 bp was ∼ 1.5x higher in SARS-CoV-2 than in HPV-positive samples. Reproducibility and repeatability of the method were tested on a subset of samples. A viral integration breakpoint followed by a partial genomic deletion was found in within-run replicates of HPV59-positive sample. Identified viral consensus sequence in two separate runs was >99.9 % identical between replicates, differing by a couple of nucleotides identified in only one of the replicates. Conversely, the number of identical minor nucleotide variants (MNVs) differed greatly between replicates, probably caused by PCR-introduced bias. The total number of detected MNVs, calculated gene variability and mutational signature analysis, were unaffected by the sequencing run.ConclusionTaME-seq2 proved well suited for consensus sequence identification, and the detection of low-frequency viral genome variation and viral-chromosomal integrations. The repertoire of TaME-seq2 now encompasses seven HR-HPV types. Our goal is to further include all HR-HPV types in the TaME-seq2 repertoire. Moreover, with a minor modification of previously developed primers, the same method was successfully applied for the analysis of SARS-CoV-2 positive samples, implying the ease of adapting TaME-seq2 to other viruses.
Assessing the availability of Repurposed Orphan Drugs in India
Authors: Rajueni Khujith , Chakraborty Choudhury Mohua 
Published: December 2022

AbstractIndia has a massive burden of rare diseases (RDs), estimated to be around 96 million living patients but limited options for treatment. Drugs used for RDs are known as Orphan Drugs. Globally, 95% of RDs do not have an approved drug for treatment. Novel orphan drugs are characteristically expensive and out of reach for most Indian patients. Repurposing drugs used for other common conditions have been considered an essential alternative for RDs due to their cost-effectiveness and reduced timeline resulting in higher success rates than novel drugs. India’s patent regime prevents the evergreening of drugs, and a large generic manufacturing industry provides ample opportunity to explore the potential of repurposed drugs for treating RDs. However, information on the availability of repurposed orphan drugs (RODs) in India is limited. Also, there is no portal for information on orphan drugs in India. This study assesses the availability of RODs in India through quantitative empirical analysis. In the absence of a separate orphan drug designation in India, we consider USFDA-approved orphan-designated products as the reference. We searched for the availability of FDA-approved RODs in recognized sources in India, such as CDSCO, AYUSH gazette, and Indian Pharmacopeia, which provides a list of drugs approved for marketing in India. We classified the drugs into separate groups based on their availability in different sources and explored the regulatory implications of the differential representations. We found that 76% of RODs approved by the USFDA are entirely or partially available in India. Information on RODs will help relevant stakeholders in the better management of RDs in India.
Benefits of sphingosine-1-phosphate receptor modulators in relapsing MS estimated with a treatment sequence model
Authors: Corsten Cato E.A. , Huygens Simone A. , Versteegh Matthijs M. , Wokke Beatrijs H.A. , Smets Ide , Smolders Joost 
Published: December 2022

AbstractBackgroundThree sphingosine-1-phosphate receptor (S1PR) modulators are currently available as disease-modifying therapies (DMTs) for relapsing MS in the Netherlands (i.e. fingolimod, ozanimod and ponesimod). We aimed to identify which S1PR modulator yields the highest benefit from a health-economic and societal perspective during a patient’s lifespan.MethodsIncorporating Dutch DMT list prices, we used the ErasmusMC/iMTA MS model to compare DMT sequences, including S1PR modulators and eight other DMT classes, for treatment-naive patients with relapsing MS in terms of health outcomes (number of lifetime relapses, time to Expanded Disability Status Scale (EDSS) 6, lifetime quality-adjusted life years (QALYs)) and cost-effectiveness (net health benefit (NHB)). We estimated the influence of list price and EDSS progression on cost-effectiveness outcomes.ResultsIn deterministic and probabilistic analysis, DMT sequences with ponesimod have lower lifetime costs and higher QALYs resulting in a higher average NHB compared to sequences with other S1PR modulators. Ponesimod remains the most cost-effective S1PR modulator when EDSS progression is class-averaged. Given the variable effects on disability progression, list price reductions could make fingolimod but not ozanimod more cost-effective than ponesimod.ConclusionOur model favours ponesimod among the S1PR modulators for the treatment of relapsing MS. This implies that prioritizing ponesimod over other S1PR modulators translates into a more efficacious spending of national healthcare budget without reducing benefit for people with MS. Prioritizing cost-effective choices when counselling patients contributes to affordable and accessible MS care.HighlightsDisease-modifying therapies (DMTs) are the largest cost driver in MSThree sphingosine-1-phosphate receptor (S1PR) modulators are used for relapsing MSOur model compares sequences of up to 5 DMTs in terms of health (relapses, progression) and costsComparing sequences including S1PR modulators, ponesimod is the most cost-effective drugCost-effectiveness research helps to prioritize when prescribing drugs of a similar class