bluuebunny/crossref_metadata_2025 huggingface dataset:
Diatom cell-size composition as a novel tool for quantitative estimates of the water table in peatlands
Authors: Xu Shuangyu , Huang Bing , Zeng Linghan , Bu Zhao-Jun , Huang Xianyu , Chen Xu
Published: June 2024

Diatom cell-size composition is an indicator of aquatic environmental changes but has been rarely investigated, especially in semi-terrestrial peatlands. In this study, both taxonomic composition and cell-size composition of diatoms were analysed in 41 samples from two montane peatlands, northeastern China. Redundancy analyses revealed that diatom taxonomic composition was significantly related to the depth to the water table (DWT) and Ca
2+
, while cell-size composition was significantly associated with DWT and Si. DWT was the most important factor and its sole effect explained 26.2% and 17.9% of the total variance in taxonomic composition and cell-size composition, respectively. Accordingly, diatom-based water-table transfer functions were developed based on taxonomic composition and cell-size composition, respectively. The maximum-likelihood (ML) model based on diatom taxonomic composition had the best performance, with a correlation coefficient value (
R
2
) of 0.78 and the root mean squared error of prediction (RMSEP) of 6.66 cm. The ML model based on cell-size composition had similar performance, with an
R
2
of 0.78 and the RMSEP of 6.87 cm, suggesting that diatom cell-size composition can be a new quantitative means to track past water-table changes. This method requires further appraisal with palaeoecological data but offers a new option that deserves exploration.
Computer simulation study of nutrient-driven bacterial biofilm stratification
Authors: Lobo-Cabrera Francisco Javier , Herrero María del Río , Govantes Fernando , Cuetos Alejandro
Published: June 2024

Here, employing computer simulation tools, we present a study on the development of a bacterial biofilm from a single starter cell on a flat inert surface overlaid by an aqueous solution containing nutrients. In our simulations, surface colonization involves an initial stage of two-dimensional cell proliferation to eventually transition to three-dimensional growth leading to the formation of biofilm colonies with characteristic three-dimensional semi-ellipsoids shapes. Thus, we have introduced the influence of the nutrient concentration on bacterial growth, and calculated the cell growth rate as a function of nutrient uptake, which in turn depends on local nutrient concentration in the vicinity of each bacterial cell. Our results show that the combination of cell growth and nutrient uptake and diffusion leads to the formation of stratified colonies containing an inner core in which nutrients are depleted and cells cannot grow or divide, surrounded by an outer, shallow crust in which cells have access to nutrients from the bulk medium and continue growing. This phenomenon is more apparent at high uptake rates that enable fast nutrient depletion. Our simulations also predict that the shape and internal structure of the biofilm are largely conditioned by the balance between nutrient diffusion and uptake.
Human performance in virtual stabilization of a fractional-order system with reaction delay
Authors: Balogh Tamas , Kovacs Balazs A. , Insperger Tamas
Published: June 2024

Virtual balancing tasks facilitate the study of human motion control: human reaction to the change of artificially introduced parameters can be studied in a computer environment. In this article, the dynamics of human stick balancing are generalized using fractional-order derivatives. Reaction delay sets a strong limitation on the length of the shortest stick that human subjects can balance. Human processing of visual input also exhibits a memory effect, which can be modelled by fractional-order derivatives. Therefore, we hypothesize a delayed fractional-order PD control of the unstable fractional-order process. The resulting equation of motion is investigated in a dimensionless framework, and stabilizability limits are determined as a function of the dynamics’s order. These theoretical limits are then compared with the results of a systematic series of virtual balancing tests performed by 18 subjects. The comparison shows that the theoretical stabilizability limits for controllers with fixed fractional order correspond to the measured data points. The best fit is obtained if the fractional order of the underlying control law is 0.475.
A comprehensive phylogeny and revised taxonomy of Diadectomorpha with a discussion on the origin of tetrapod herbivory
Authors: Ponstein Jasper , MacDougall Mark J. , Fröbisch Jörg
Published: June 2024

Among terrestrial tetrapods, the origin of herbivory marked a key evolutionary event that allowed for the evolution of modern terrestrial ecosystems. A 100 Ma gap separates the oldest terrestrial tetrapods and the first undisputed herbivorous tetrapods. While four clades of early tetrapod herbivores are undisputed amniotes, the phylogenetic position of Diadectomorpha with respect to Amniota has long been controversial. Given that the origin of herbivory coincides with the oldest amniotes, and obligate herbivory is unknown within amphibians, this suggests that a key adaptation necessary to evolve obligate herbivory is unique to amniotes. Historically, phylogenetic analyses have found Diadectomorpha as the sister-group to amniotes, but recent analyses recover Diadectomorpha as sister-group to Synapsida, within Amniota. We tested whether diadectomorphs are amniotes by updating the most recent character–taxon matrix. Specifically, we added new characters from the lower jaw and added diadectomorph taxa, resulting in a dataset of 341 characters and 61 operational taxonomic units. We updated the description of five diadectomorph jaws using microcomputed tomography data. Our majority-rule consensus places Diadectomorpha as sister-group to Synapsida; other methods do not recover this relationship. We revise diadectomorph taxonomy, erecting a new species from the early Permian Bromacker locality, Germany, and a new genus to accommodate ‘
Diadectes’ sanmiguelensis
.
Inoculation hesitancy: an exploration of challenges in scaling inoculation theory
Authors: Johnson Alexandra , Madsen Jens Koed
Published: June 2024

Inoculation theory research offers a promising psychological ‘vaccination’ against misinformation. But are people willing to take it? Expanding on the inoculation metaphor, we introduce the concept of ‘inoculation hesitancy’ as a framework for exploring reluctance to engage with misinformation interventions. Study 1 investigated whether individuals feel a need for misinformation inoculations. In a comparative self-evaluation, participants assessed their own experiences with misinformation and expectations of inoculation and compared them to those of the average person. Results exposed a better-than-average effect. While participants were concerned over the problem of misinformation, they estimated that they were less likely to be exposed to it and more skilful at detecting it than the average person. Their self-described likelihood of engaging with inoculation was moderate, and they believed other people would benefit more from being inoculated. In Study 2, participants evaluated their inclination to watch inoculation videos from sources varying in trustworthiness and political affiliation. Results suggest that participants are significantly less willing to accept inoculations from low-trust sources and less likely to accept inoculations from partisan sources that are antithetical to their own political beliefs. Overall, this research identifies motivational obstacles in reaching herd immunity with inoculation theory, guiding future development of inoculation interventions.
How frequently are insects wounded in the wild? A case study using
Drosophila melanogaster
Authors: Subasi Bengisu S. , Grabe Veit , Kaltenpoth Martin , Rolff Jens , Armitage Sophie A. O.
Published: June 2024

Wounding occurs across multicellular organisms. Wounds can affect host mobility and reproduction, with ecological consequences for competitive interactions and predator–prey dynamics. Wounds are also entry points for pathogens. An immune response is activated upon injury, resulting in the deposition of the brown-black pigment melanin in insects. Despite the abundance of immunity studies in the laboratory and the potential ecological and evolutionary implications of wounding, the prevalence of wounding in wild-collected insects is rarely systematically explored. We investigated the prevalence and potential causes of wounds in wild-collected Drosophilidae flies. We found that 31% of
Drosophila melanogaster
were wounded or damaged. The abdomen was the most frequently wounded body part, and females were more likely to have melanized patches on the ventral abdomen, compared with males. Encapsulated parasitoid egg frequency was approximately 10%, and just under 1% of Drosophilidae species had attached mites, which also caused wounds. Wounding is prevalent in
D. melanogaster
, likely exerting selection pressure on host immunity for two reasons: on a rapid and efficient wound repair and on responding efficiently to opportunistic infections. Wounding is thus expected to be an important driver of immune system evolution and to affect individual fitness and population dynamics.
Shifting norms, static behaviour: effects of dynamic norms on meat consumption
Authors: Aldoh Alaa , Sparks Paul , Harris Peter R.
Published: June 2024

While decreasing their meat consumption is one of the most impactful behaviours an individual may carry out to reduce their carbon emissions, it is still a minority behaviour in many parts of the world. Research suggests that communicating information about changing ‘dynamic’ norms may be a useful tool for changing attitudes and behaviours in the direction of those currently held by the minority. This study uses a 2 × 2 mixed design (norm type [dynamic/static] × visual cue [present/absent, and a no-task control), and a follow-up assessment after one week to investigate the effect of making dynamic norms salient on various meat consumption outcomes: attitudes towards meat consumption, interest in reducing one’s own meat consumption, intentions to reduce one’s own meat consumption and self-reported meat consumption. We used an online sample of British participants (
N
= 1294), ranging in age 18–77 (
M
age
= 39.97, s.d.
age
= 13.71; 55.8% female). We hypothesized that: (i) dynamic norms will positively influence meat consumption outcomes; (ii) visual cues will accentuate the difference between norm conditions; (iii) using a visual cue will enhance the effect of dynamic norms; and (iv) any effects of dynamic norms will endure over a period of one week. We found no positive effect of dynamic norms (versus static norms) on any outcome at time 1, and no positive effect on changes in outcomes from time 1 to time 2. However, we found a positive interaction of norm type and visual cue at time 1 (although not from time 1 to time 2): the addition of a visual cue to dynamic norm messages enhanced the positive effect of the message at time 1 (but did not enhance the changes occurring from time 1 to time 2). Analyses for changes in self-reported meat consumption did not reach our evidential threshold. We discuss the practical and theoretical implications of these findings.
Host ecotype and rearing environment are the main drivers of threespine stickleback gut microbiota diversity in a naturalistic experiment
Authors: Härer Andreas , Frazier Christine J. , Rennison Diana J.
Published: June 2024

Host–microbiota interactions play a critical role in the hosts’ biology, and thus, it is crucial to elucidate the mechanisms that shape gut microbial communities. We leveraged threespine stickleback fish (
Gasterosteus aculeatus
) as a model system to investigate the contribution of host and environmental factors to gut microbiota variation. These fish offer a unique opportunity for experiments in naturalistic conditions; we reared benthic and limnetic ecotypes from three different lakes in experimental ponds, allowing us to assess the relative effects of shared environment (pond), geographic origin (lake-of-origin), trophic ecology and genetics (ecotype) and biological sex on gut microbiota α- and β-diversity. Host ecotype had the strongest influence on α-diversity, with benthic fish exhibiting higher diversity than limnetic fish, followed by the rearing environment. β-diversity was primarily shaped by rearing environment, followed by host ecotype, indicating that environmental factors play a crucial role in determining gut microbiota composition. Furthermore, numerous bacterial orders were differentially abundant across ponds, underlining the substantial contribution of environmental factors to gut microbiota variation. Our study illustrates the complex interplay between environmental and host ecological or genetic factors in shaping the stickleback gut microbiota and highlights the value of experiments conducted under naturalistic conditions for understanding gut microbiota dynamics.
Multi-talker speech comprehension at different temporal scales in listeners with normal and impaired hearing
Authors: Li Jixing , Wang Qixuan , Zhou Qian , Yang Lu , Shen Yutong , Huang Shujian , Wang Shaonan , Pylkkänen Liina , Huang Zhiwu
Published: June 2024

Comprehending speech requires deciphering a range of linguistic representations, from phonemes to narratives. Prior research suggests that in single-talker scenarios, the neural encoding of linguistic units follows a hierarchy of increasing temporal receptive windows. Shorter temporal units like phonemes and syllables are encoded by lower-level sensory brain regions, whereas longer units such as sentences and paragraphs are processed by higher-level perceptual and cognitive areas. However, the brain’s representation of these linguistic units under challenging listening conditions, such as a cocktail party situation, remains unclear. In this study, we recorded electroencephalogram (EEG) responses from both normal-hearing and hearing-impaired participants as they listened to individual and dual speakers narrating different parts of a story. The inclusion of hearing-impaired listeners allowed us to examine how hierarchically organized linguistic units in competing speech streams affect comprehension abilities. We leveraged a hierarchical language model to extract linguistic information at multiple levels—phoneme, syllable, word, phrase, and sentence—and aligned these model activations with the EEG data. Our findings showed distinct neural responses to dual-speaker speech between the two groups. Specifically, compared to normal-hearing listeners, hearing-impaired listeners exhibited poorer model fits at the acoustic, phoneme, and syllable levels as well as the sentence levels, but not at the word and phrase levels. These results suggest that hearing-impaired listeners experience disruptions at both shorter and longer temporal scales, while their processing at medium temporal scales remains unaffected.
ClearFinder: a Python GUI for annotating cells in cleared mouse brain
Authors: Pastore Stefan , Hillenbrand Philipp , Molnar Nils , Kovlyagina Irina , Chongtham Monika Chanu , Sys Stanislav , Lutz Beat , Tevosian Margarita , Gerber Susanne
Published: June 2024

Background

Tissue clearing combined with light-sheet microscopy is gaining popularity among neuroscientists interested in unbiased assessment of their samples in 3D volume. However, the analysis of such data remains a challenge. ClearMap and CellFinder are tools for analyzing neuronal activity maps in an intact volume of cleared mouse brains. However, these tools lack a user interface, restricting accessibility primarily to scientists proficient in advanced Python programming. The application presented here aims to bridge this gap and make data analysis accessible to a wider scientific community.

Results

We developed an easy-to-adopt graphical user interface for cell quantification and group analysis of whole-cleared adult mouse brains. Fundamental statistical analysis, such as PCA and box plots, and additional visualization features allow for quick data evaluation and quality checks. Furthermore, we report significant differences in total cell counts between CellFinder and ClearMap when cross-analyzing the same samples, underscoring the need for optimizing reproducibility within the field.

Conclusions

Our easily accessible tool allows more researchers to implement the methodology, troubleshoot arising issues, and develop quality checks, benchmarking, and standardized analysis pipelines for cell detection and region annotation in whole volumes of cleared brains.
Information transmission in a cell monolayer: A numerical study
Authors: Nałęcz-Jawecki Paweł , Szyc Przemysław , Grabowski Frederic , Kochańczyk Marek , Lipniacki Tomasz
Published: June 2024

Motivated by the spatiotemporal waves of MAPK/ERK activity, crucial for long-range communication in regenerating tissues, we investigated stochastic homoclinic fronts propagating through channels formed by directly interacting cells. We evaluated the efficiency of long-range communication in these channels by examining the rate of information transmission. Our study identified the stochastic phenomena that reduce this rate: front propagation failure, new front spawning, and variability in the front velocity. We found that a trade-off between the frequencies of propagation failures and new front spawning determines the optimal channel width (which geometrically determines the front length). The optimal frequency of initiating new waves is determined by a trade-off between the input information rate (higher with more frequent initiation) and the fidelity of information transmission (lower with more frequent initiation). Our analysis provides insight into the relative timescales of intra- and intercellular processes necessary for successful wave propagation.

Author Summary

In biological tissues, traveling waves of cellular activity are observed in the process of wound healing when they coordinate cell replication and collective migration. These waves can carry information over long distances. However, random effects on the single-cell level can affect wave propagation and disrupt information flow. In this paper, using a numerical model we classified these stochastic events and quantified the maximum range and frequency of such waves and their capacity to carry information. We discovered that most effective transmission occurs in relatively narrow channels (formed by directly interacting cells), and that the refractory time, in which a cell is resistant to activation by neighboring cells, must be long with respect to the time needed for cell activation. The optimal time intervals between the initiated waves are of order of few refractory times (depending on channel length).
High-resolution quantification of the rhizosphere effect along a soil-to-root gradient shows selection-driven convergence of rhizosphere microbiomes
Authors: Poppeliers Sanne W.M. , Sánchez-Gil Juan José , López José Luis , Dutilh Bas E. , Pieterse Corné M. J. , de Jonge Ronnie
Published: June 2024

Plants secrete a complex array of organic compounds, constituting about a third of their photosynthetic products, into the surrounding soil. As a result, concentration gradients are established from the roots into the bulk soil, known as the rhizosphere. Soil microbes benefit from these root exudates for their survival and propagation, and consequently, the composition of the rhizosphere microbial community follows the gradient of available compounds, a phenomenon oftentimes referred to as the rhizosphere effect. However, the fine-grained changes in the microbial community along this soil-root gradient have not been well described. Yet such insights would enable us to underpin the ecological rules underlying root microbial community assembly. Therefore, here we harvested the roots of individualArabidopsis thalianaplants grown in three different natural soils at high-resolution, such that we could interrogate community assembly and predict microbial growth rate across consecutive, fine-grained, rhizosphere ‘compartments’. We found that the strength of the rhizosphere effect depends on root proximity and that microbial communities closer to the roots harbour related microbes. Closer to the roots, microbial community assembly became less random and more driven by selection-based processes. Intriguingly, we observed priority effects, where related microbes that arrive first are more likely to establish, and that microbes might use different ecological growth strategies to colonise the rhizosphere. All effects appeared to be independent from starting conditions as microbial community composition converged on the root despite different soil ‘microbial seed banks’. Together, our results provide a high-resolution view of the microbiome changes across the soil-root gradient.
AML patient blasts exhibit polarization defect upon interaction with bone marrow stromal cells
Authors: Saadallah Khansa , Vianay Benoît , Bonnemay Louise , Pasquer Hélène , Kelly Lois , Culeux Cécile , Marie Raphael , Fodil Sofiane , Chaintreuil Paul , Kerreneur Emeline , Jacquel Arnaud , Raffoux Emmanuel , Nizard Rémy , Blanchoin Laurent , Benajiba Lina , Théry Manuel
Published: June 2024

Hematopoietic stem and progenitor cells (HSPCs) establish specific interactions with bone marrow stromal cells, leading to their polarization. Given the role of cell polarity in protection against tumorigenesis and the importance of the niche in hematological disorders such as acute myeloid leukemias (AMLs), we investigated the polarization capacities of leukemic blasts from patients. Using engineered micro-niches and centrosome position with respect to the contact site with stromal cells as a proxy for cell polarization, we showed that AML cell lines and primary cells from AML patient blasts were unable to polarize in contact with healthy stromal cells. In return, exposure to AML patient-derived stromal cells compromised the polarization of healthy adult HSPCs and AML blasts from patients. Using live cell imaging in engineered “bone-marrow-on-a-chip”, we further revealed that stromal cells from a leukemic niche increased the migration speed and distance of healthy HSPCs and AML blast as compared to their behavior in contact with healthy stromal cells. The results collectively demonstrated the respective influences of intrinsic AML blast transformation and extrinsic contact with AML stromal cells on the defective polarization of AML blast. They suggested that leukemic progression is associated with cell polarization defects and proposed new methodological approaches to investigate this relationship in AML progression.
Pronouns reactivate conceptual representations in human hippocampal neurons
Authors: Dijksterhuis D. E. , Self M. W. , Possel J. K. , Peters J. C. , van Straaten E.C.W. , Idema S. , Baaijen J. C. , van der Salm S. M. A. , Aarnoutse E.J. , van Klink N. C. E. , van Eijsden P. , Hanslmayr S. , Chelvarajah R. , Roux F. , Kolibius L. D. , Sawlani V. , Rollings D. T. , Dehaene S. , Roelfsema P. R.
Published: June 2024

During discourse comprehension, every new word adds to an evolving representation of meaning that accumulates over consecutive sentences and constrains the next words. To minimize repetition and utterance length, languages use pronouns, like the word ‘she’, to refer to nouns and phrases that were previously introduced. It has been suggested that language comprehension requires that pronouns activate the same neuronal representations as the nouns themselves. Here, we test this hypothesis by recording from individual neurons in the human hippocampus during a reading task. We found that cells that are selective to a particular noun are later reactivated by pronouns that refer to the cells’ preferred noun. These results imply that concept cells contribute to a rapid and dynamic semantic memory network which is recruited during language comprehension. This study uniquely demonstrates, at the single-cell level, how memory and language are linked.
Adiponectin pathway activation dampens inflammation and enhances alveolar macrophage fungal killing via LC3-associated phagocytosis
Authors: Goli Sri Harshini , Lim Joo-Yeon , Basaran-Akgul Nese , Templeton Steven P.
Published: June 2024

Although innate immunity is critical for antifungal host defense against the human opportunistic fungal pathogenAspergillus fumigatus, potentially damaging inflammation must be controlled. Adiponectin (APN) is an adipokine produced mainly in adipose tissue that exerts anti-inflammatory effects in adipose-distal tissues such as the lung. We observed 100% mortality and increased fungal burden and inflammation in neutropenic mice with invasive aspergillosis (IA) that lack APN or the APN receptors AdipoR1 or AdipoR2. Alveolar macrophages (AMs), early immune sentinels that detect and respond to lung infection, express both receptors, and APN-/- AMs exhibited an inflammatory/M1 phenotype that was associated with decreased fungal killing. Pharmacological stimulation of AMs with AdipoR agonist AdipoRon partially rescued deficient killing in APN-/- AMs that was dependent on both receptors. Finally, APN-enhanced fungal killing was associated with increased activation of the non-canonical LC3 pathway of autophagy. Thus, our study identifies a novel role for APN in LC3-mediated killing ofA.fumigatus.

Author Summary

Aspergillus fumigatusis a human fungal pathogen that causes an often-fatal invasive infection of the lung in immune compromised individuals, a population that is increasing. Since current antifungal drugs have limited efficacy, it is important to identify pathways that may be pharmaceutically targeted to complement existing therapies. Adiponectin (APN) is an anti-inflammatory intercellular cytokine messenger produced mainly in adipose tissue that protects against invasive aspergillosis. Alveolar macrophages are early immune sentinel cells in the lung, and we report that AMs from mice lacking APN exhibit an inflammatory phenotype and reduced killing ofA. fumigatusspores that is improved when AMs are treated with a drug (AdipoRon) that simulates APN binding to its receptors AdipoR1 and AdipoR2. Furthermore, APN was associated with activation of LC3-associated phagocytosis, a mechanism of fungal killing important for host defense againstA. fumigatusinfection. Thus, we identify therapeutic potential of the APN pathway in stimulation of immune-mediated fungal killing and treatment of fungal infection.
Automated high-throughput selection of DNA aptamers using a common optical next-generation sequencer
Authors: Drees Alissa , Ahlers Christian , Kehrer Timothy , Ehmke Natascha , Grün Alice Frederike Rosa , Uetrecht Charlotte , Ignatova Zoya , Schumacher Udo , Fischer Markus
Published: June 2024

Aptamers are conventionally selected via ‘Systematic Evolution of Ligands by Exponential Enrichment’ (SELEX). This process is, however, laborious, time-consuming, and has a relatively low efficacy. Here, we developed an automated high-throughput screening platform for the selection of DNA aptamers which consists of an optical next-generation sequencer with a modified software and hardware to automatically perform fluorescence-based binding assays on the displayed DNA sequences subsequent to sequencing. Using this platform, after only three to five SELEX rounds we selected highly affine DNA aptamers for the lectins LecA and LecB ofPseudomonas aeruginosaas well as for thePseudomonasExotoxin A. In comparison, twelve rounds of conventional SELEX resulted in three-fold less affine aptamers for LecA and PEA and none for LecB. Our high throughput-approach bears great potential to augment SELEX as it significantly increases time efficiency, enabling the selection of aptamers within only one week.
The DNA damage response relies on the characteristics of ionizing particles in myogenic cells
Authors: Sutcu Haser Hasan , Thomas--Joyeux Arthur , Cardot-Martin Mikaël , Vianna François , Benadjaoud Mohamed Amine , Benderitter Marc , Baldeyron Céline
Published: June 2024

DNA integrity and stability are vital for proper cellular activity. Nevertheless, to treat cancer patients, DNA is the main target for inducing tumoral cell death. Nowadays, cancer treatment is improving by the development of new technologies, protocols and strategies. Amongst them, the introduction of charged particles as a form of radiotherapy is underway. However, tumor-neighboring healthy tissues are still exposed to ionizing radiations (IR) and subject to late side effects. Skeletal muscle is one of those tissues most likely to be affected. To decipher the DNA damage response (DDR) of skeletal muscle cells, myogenic cells, we irradiated them with microbeams of protons or α-particles and followed the accumulation of DDR proteins at irradiation sites. Thereby, we showed that myoblasts, proliferating myogenic cells, repair IR-induced DNA damage through both non-homologous end-joining and homologous recombination with different recruitment dynamics depending on the characteristics of ionizing particles (type, energy deposition and time after irradiation), whereas myotubes, post-mitotic myogenic cells, display reduced DNA damage response.

Mouse skeletal muscle cells and their precursor cells irradiated by ion microbeam show DNA damage response and DNA repair dynamics that vary according to the characteristics of ionizing particles delivered.

Graphical Abstract
Thalamocortical contributions to hierarchical cognitive control
Authors: Chen Xitong , Leach Stephanie C. , Hollis Juniper , Cellier Dillan , Hwang Kai
Published: June 2024

Cognitive flexibility relies on hierarchically structured task representations that organize task contexts, relevant environmental features, and subordinate decisions. Despite ongoing interest in the human thalamus, its role in cognitive control has been understudied. This study explored thalamic representation and thalamocortical interactions that contribute to hierarchical cognitive control in humans. We found that several thalamic nuclei, including the anterior, mediodorsal, ventrolateral, and pulvinar nuclei, exhibited stronger evoked responses when subjects switch between task contexts. Decoding analysis revealed that thalamic activity encodes task contexts within the hierarchical task representations. To determine how thalamocortical interactions contribute to task representations, we developed a thalamocortical functional interaction model to predict task-related cortical representation. This data-driven model outperformed comparison models, particularly in predicting activity patterns in cortical regions that encode context representations. Collectively, our findings highlight the significant contribution of thalamic activity and thalamocortical interactions for contextually guided hierarchical cognitive control.
Visual search efficiency is modulated by symmetry type and texture regularity
Authors: Moreau Rachel , Alp Nihan , Clarke Alasdair DF , Freud Erez , Kohler Peter J.
Published: June 2024

More than a century of vision research has identified symmetry as a fundamental cue, which aids the visual system in making inferences about objects and surfaces in natural scenes. Most studies have focused on one type of symmetry, reflection, presented at a single image location. However, the visual system responds strongly to other types of symmetries, and to symmetries that are repeated across the image plane to form textures. Here we use a visual search paradigm with arrays of repeating lattices that contained either reflection or rotation symmetries but were otherwise matched. Participants were asked to report the presence of a target tile without symmetry. When lattices tile the plane without gaps, they form regular textures. We manipulated texture regularity by introducing jittered gaps between lattices. This paradigm lets us investigate the effect of symmetry type and texture regularity on visual search efficiency. Based on previous findings suggesting an advantage for reflection in visual processing, we hypothesized that search would be more efficient for reflection than rotation. We further hypothesized that regular textures would be processed more efficiently. We found independent effects of symmetry type and regularity on search efficiency that confirmed both hypotheses: visual search was more efficient for textures with reflection symmetry and more efficient for regular textures. This provides additional support for the perceptual advantage of reflection in the context of visual search and provides important new evidence in favor of visual mechanisms specialized for processing symmetries in regular textures.
Replicative senescence is ATM driven, reversible, and accelerated by hyperactivation of ATM at normoxia
Authors: Stuart Alexander , de Lange Titia
Published: June 2024

Programmed telomere shortening limits tumorigenesis through the induction of replicative senescence. Here we address three long-standing questions concerning senescence. First, we show that the ATM kinase is solely responsible for the induction of replicative senescence. Senescence was delayed by ATM inhibition (ATMi) or overexpression of TRF2, the shelterin subunit dedicated to ATM repression. In contrast, there was no evidence for ATR signaling contributing to replicative senescence even when ATMi was combined with ATR inhibition. Second, we show ATMi can induce apparently normal cell divisions in a subset of senescent cells, indicating that senescence can be reversed. Third, we show that the extended replicative life span at low (physiological) oxygen is due to diminished ATM activity. At low oxygen, cells show a decreased ATM response to dysfunctional telomeres and genome-wide DSBs compared to 20% oxygen. As this effect could be reversed by NAC, the attenuated response of ATM to critically short telomeres and the resulting extended life span at low oxygen is likely due to ROS-induced formation of cysteine disulfide-bridges that crosslink ATM dimers into a form that is not activated by DSBs. These findings show how primary human cells detect shortened telomeres and reveal the molecular mechanism underlying the telomere tumor suppressor pathway.
Reliability and criterion validity of a low-cost handgrip dynamometer: The Camry
Authors: Sánchez-Aranda Lucía , Fernández-Ortega Javier , Martín-Fuentes Isabel , Toval Ángel , Jurak Gregor , Ruiz Jonatan R , Csányi Tamás , Ortega Francisco B.
Published: June 2024

Background

Handgrip strength has been related with multiple health outcomes, including all-cause mortality and morbidity. Handgrip testing is a highly valid and reliable method, included in evidence-based fitness test batteries from preschool to older ages. Previously, Jamar and TKK dynamometers have shown good reliability and validity against known weights. However, the cost of these dynamometers is the major limitation for implementing handgrip strength testing in certain countries and settings, as well as at large scale. Recently, a ten times cheaper model (Camry Dynamometer) has been used in fitness surveillance systems, though its reliability and validity, compared to known weights and other well-validated dynamometers, remains unknown. Therefore, the aims of the current study were to test to examine test-retest reliability, inter-model reliability (comparing a Camry dynamometer with 3000 uses versus a new Camry dynamometer), and inter-instrument reliability (Camry versus TKK dynamometer) of Camry dynamometer, using calibrated known weights.

Methods

A digital TKK 5401 dynamometer and two Camry EH101, a new and an “old” (3000 uses), dynamometers were used. Intra-instrument and inter-instrument reliability, and criterion related validity were assessed comparing the measures of the dynamometers with calibrated weights using the Bland and Altman’s method.

Results

Intra-instrument (retest minus test) reliability was very high (systematic error for test-retest reliability: New Camry = 0.01±0.49kg; Old Camry = -0.10±0.49kg; TKK = 0.14±0.77kg). The comparison between instruments showed small mean differences between Camry dynamometers and TKK (New Camry VS TKK: 0.84±0.79kg; Old Camry VS TKK: 0.88 ±0.85kg). The systematic error between New and Old Camry dynamometers was 0.03±0.57kg. Criterion-related validity showed smaller magnitude systematic errors in the Camry than TKK instruments (New Camry: -0.21±0.35kg; Old Camry: -0.18±0.79kg; TKK: -1.07±0.75kg).

Conclusions

Our results support that Camry dynamometer has an excellent reliability and validity and is therefore a more affordable alternative for handgrip strength assessment. Our results also indicate a good durability of these devices, and that calibration is not necessary, even after several thousands of uses.
The association between age and high-intensity treatment in traumatic brain injury patients: a CENTER-TBI study
Authors: van Veen Ernest , Kompanje Erwin J. O. , van der Jagt Mathieu , Mikolić Ana , Citerio Giuseppe , Stocchetti Nino , Gommers Diederik , Menon David K. , Maas Andrew I. R. , Lingsma Hester F. ,   the CENTER-TBI investigators and participants
Published: June 2024

Introduction

Older age is associated with worse outcome after traumatic brain injury (TBI). Whether this association is entirely driven by frailty, or clinicians’ reluctance to give specific treatments to older patients is unclear. Therefore, we aimed to confirm the association between age and worse outcome, and to assess the association between age and received high-intensity treatment (HIT).

Methods

We included TBI patients aged 16 and older from the CENTER-TBI study. The association between age and HIT, and between age and outcome (the Glasgow Outcome Scale Extended (GOSE) at 6 months), was analyzed using multivariable ordinal and logistic regression respectively. In the overall cohort, HIT was defined as receiving emergency intracranial surgery, or ICU admission. In the subset of patients admitted to the ICU, HIT was defined as receiving metabolic suppression, intensive hypocapnia, hypothermia below 35 °C, decompressive craniectomy, or intracranial surgery not scheduled on admission. We adjusted for pre-injury health, injury severity (Glasgow Coma Scale (GCS) motor score and pupillary reactivity at baseline; major extracranial injury (MEI); Marshall CT classification), and in the subset of ICU patients for the median ICP before receiving any HIT.

Results

In total, 4349 patients were included. Of these, 1999 patients (46%) were admitted to the ICU. The median age was 51 years. Every ten-year increase in age for patients over 65, was associated with worse outcome (OR = 0.6, CI = 0.5 – 0.7, OR in the subset of ICU patients = 0.5, CI = 0.3 – 0.5). Furthermore, every ten-year increase in age for patients over 65 was associated with a lower likelihood of receiving emergency intracranial surgery (OR = 0.4, CI = 0.3 – 0.6), and ICU admission (OR = 0.6, CI = 0.5 – 0.8). Similarly, in the subset of ICU patients, every ten-year increase in age for patients over 65, was associated with a lower likelihood of receiving neuromuscular blockade (OR = 0.6, CI = 0.4 – 0.9), intensive hypocapnia (OR = 0.2, CI = 0.1 – 0.9), decompressive craniectomy (OR = 0.4, CI = 0.2 – 0.8), and intracranial surgery (OR = 0.5, CI = 0.3 – 0.8).

Conclusion

Older patients have poorer outcome, and were less likely to receive high-intensity treatments, independent of patient and injury characteristics. Clinicians should not withhold high-intensity treatments solely based on older age. Educating clinicians about this delicate topic, and performing further comparative effectiveness research focusing on older patients may improve diagnosis, treatments, and understanding of TBI outcomes in this group.
Improving postsurgical fall detection for older Americans using LLM-driven analysis of clinical narratives
Authors: Pillai Malvika , Blumke Terri L , Studnia Joachim , Wang Yuqing , Veigulis Zachary P , Ware Anna D , Hoover Peter J , Carroll Ian R , Humphreys Keith , Osborne Thomas F , Asch Steven M. , Hernandez-Boussard Tina , Curtin Catherine M
Published: June 2024

Postsurgical falls have significant patient and societal implications but remain challenging to identify and track. Detecting postsurgical falls is crucial to improve patient care for older adults and reduce healthcare costs. Large language models (LLMs) offer a promising solution for reliable and automated fall detection using unstructured data in clinical notes. We tested several LLM prompting approaches to postsurgical fall detection in two different healthcare systems with three open-source LLMs. The Mixtral-8×7B zero-shot had the best performance at Stanford Health Care (PPV = 0.81, recall = 0.67) and the Veterans Health Administration (PPV = 0.93, recall = 0.94). These results demonstrate that LLMs can detect falls with little to no guidance and lay groundwork for applications of LLMs in fall prediction and prevention across many different settings.
Efficient blockLASSO for Polygenic Scores with Applications to All of Us and UK Biobank
Authors: Raben Timothy G. , Lello Louis , Widen Erik , Hsu Stephen D.H.
Published: June 2024

We develop a “block” LASSO (blockLASSO) method for training polygenic scores (PGS) and demonstrate its use in All of Us (AoU) and the UK Biobank (UKB). BlockLASSO utilizes the approximate block diagonal structure (due to chromosomal partition of the genome) of linkage disequilibrium (LD). LASSO optimization is performed chromosome by chromosome, which reduces computational complexity by orders of magnitude. The resulting predictors for each chromosome are combined using simple re-weighting techniques. We demonstrate that blockLASSO is generally as effective for training PGS as (global) LASSO and other approaches. This is shown for 11 different phenotypes, in two different biobanks, and across 5 different ancestry groups (African, American, East Asian, European, and South Asian). The block approach works for a wide variety of pheno-types. In the past, it has been shown that some phenotypes are more/less polygenic than others. Using sparse algorithms, an accurate PGS can be trained for type 1 diabetes (T1D) using 100 single nucleotide variants (SNVs). On the other extreme, a PGS for body mass index (BMI) would need more than 10k SNVs. blockLasso produces similar PGS for phenotypes while training with just a fraction of the variants per block. For example, within AoU (using only genetic information) block PGS for T1D (1,500 cases/113,297 controls) reaches an AUC of 0.63±0.02and for BMI (102,949 samples) a correlation of 0.21±0.01. This is compared to a traditional global LASSO approach which finds for T1D an AUC 0.65±0.03and BMI a correlation 0.19±0.03. Similar results are shown for a total of 11 phenotypes in both AoU and the UKB and applied to all 5 ancestry groups as defined via an Admixture analysis. In all cases the contribution from common covariates – age, sex assigned at birth, and principal components – are removed before training. This new block approach is more computationally efficient and scalable than global machine learning approaches. Genetic matrices are typically stored as memory mapped instances, but loading a million SNVs for a million participants can require 8TB of memory. Running a LASSO algorithm requires holding in memory at least two matrices this size. This requirement is so large that even large high performance computing clusters cannot perform these calculations. To circumvent this issue, most current analyses use subsets: e.g., taking a representative sample of participants and filtering SNVs via pruning and thresholding. High-end LASSO training uses ∼ 500 GB of memory (e.g., ∼ 400k samples and ∼ 50k SNVs) and takes 12-24 hours to complete. In contrast, the block approach typically uses ∼ 200× (2 orders of magnitude) less memory and runs in ∼ 500× less time.
Identifying real-time surveillance indicators that can be used to estimate COVID-19 hospital admissions
Authors: Grover Elise N. , Hill Andrew , Kasarskis Irina M. , Wu Emma J. , Alden Nisha , Cronquist Alicia B. , Weisbeck Kirsten , Herlihy Rachel , Carlton Elizabeth J.
Published: June 2024

Numerous approaches have been used to track COVID-19 trends, from wastewater surveillance to laboratory reporting of diagnostic test results. However, questions remain about how best to focus surveillance efforts during and after public health emergencies. Using an archive of SARS-CoV-2 surveillance data, we reconstructed seven real-time surveillance indicators and assessed their performance as predictors of 7-day moving average COVID-19 hospital admissions in Colorado from October 2020 to March 2024. Models were constructed using neural network models and Ordinary Least Squares regression. We found that hospital census data, emergency-department based syndromic surveillance, and daily COVID-19 hospital admissions were the best indicators of COVID-19 hospital demand in Colorado during the public health emergency (PHE) (October 2020 – May 2023) and after (May 2023 – March 2024). The removal of wastewater from our multi-indicator models resulted in a decrease in model performance, indicating that wastewater provides important and unique information. By contrast, capacity to predict COVID-19 hospital admissions was not meaningfully reduced when sentinel test positivity, statewide test positivity, and/or case report data were dropped from our prediction models during and after the PHE. These findings underscore the importance of hospital-based reporting for monitoring COVID-19 hospital admissions, and, conversely, suggest that case reporting and percent positivity are not essential to monitoring COVID-19 hospitalizations in Colorado.
Atrial fibrillation, venous thromboembolism, and risk of pulmonary hypertension: A Swedish Nationwide Register Study
Authors: Hjalmarsson Clara , Lindgren Martin , Bergh Niklas , Hornestam Björn , Smith J. Gustav , Adiels Martin , Rosengren Annika
Published: June 2024

Background

Atrial fibrillation (AF) is a recognized risk factor for systemic arterial- and venous thromboembolism (VTE), including pulmonary embolism (PE), and may thereby contribute to the development of chronic thrombo-embolic pulmonary hypertension (PH). AF may also play a direct role in the development of post-capillary PH. We aimed to investigate the association between AF - with or without incident VTE - and the occurrence of PH.

Methods

A total of 521 988 patients diagnosed with AF between 1987–2013, without a previous diagnosis of VTE or PH, were identified from the Swedish National Patient Register (NPR) and matched for age, sex, and county with 1 017 277 population controls without AF, VTE or PH.

Results

The mean age of the AF patients was 71.1 (SD ±10.1) years and 42.8 % were women. During a median follow-up period of 11 (IQR 5.1,17) years, 4 454 (0.9%) AF patients and 1 855 (0.2%) controls were diagnosed with PH, HR 4.7 (4.4-5.0). The AF group had a significantly higher comorbidity burden at baseline, with a mean CHA2DS2-VASc of 2.9 compared to 2.1 in controls. In the absence of intercurrent VTE, the HR of PH was 4.2 (3.9-4.5) among AF patients compared to controls. Intercurrent VTE increased the HR of PH a further 1.9-fold (1.7-2.1) and 3.5 (3.1-4.0), among AF patients and controls, respectively. The HR for PH in AF patients with incident VTE was 8.1 (7.3-9.1).

Conclusion

AF was associated with a markedly increased risk of developing incident PH, and this risk was further increased by incident VTE.