bluuebunny/crossref_metadata_2025 huggingface dataset:
Eye Tracking during Passage Reading Supports Precise Oculomotor Assessment in Ataxias
Authors: Oubre Brandon , Yang Faye , Luddy Anna C. , Manohar Rohin , Soja Nancy N. , Stephen Christopher D. , Schmahmann Jeremy D. , Kulkarni Divya , White Lawrence , Patel Siddharth , Gupta Anoopum S.
Published: January 2025

Abnormal eye movements occur early in the course of disease in many ataxias. However, clinical assessments of oculomotor function lack precision, limiting sensitivity for measuring progression and the ability to detect subtle early signs. Quantitative assessment of eye movements during everyday behaviors such as reading has potential to overcome these limitations and produce functionally relevant measures.

In this study, we analyze eye movements in individuals with ataxia during passage reading. Binocular gaze sampled at 1000 Hz was collected from 102 individuals with ataxia diagnoses (including 36 spinocerebellar ataxias, 12 Friedreich’s ataxia, and 5 multiple system atrophy among other conditions) and 70 healthy controls participating in the Neurobooth study. Longitudinal data were available for 26 participants with ataxia. Saccades were categorized as progressive (rightward) saccades, regressive saccades, or sweeps (large displacement saccades primarily generated when scanning to the beginning of the next line) based on their direction and displacement. Saccade and fixation kinematics were summarized using 28 statistical features. A linear model was trained to estimate clinician-performed ataxia rating scale scores.

Model scores were reliable (ICC=0.96, p<0.001) and demonstrated convergent validity with Brief Ataxia Rating Scale total (r=0.82, p<0.001), oculomotor (r=0.52, p<0.001), and speech (r=0.73, p<0.001) scores, as well as patient surveys. The scores were also sensitive to disease progression (d=0.36, p=0.03), demonstrated strong separability between healthy controls and participants with ataxias (AUC=0.89, p<0.001), and showed evidence of the ability to detect subclinical oculomotor patterns (AUC=0.69, p=0.02). Several kinematic saccade and fixation features demonstrated strong differences across disease severity groups. Notable features included the mean angular displacement of fixations (η2=0.44, p<0.001), the number (η2=0.27, p<0.001) and frequency of saccades (η2=0.25, p<0.001), and the proportion of regressive saccades (η2=0.11, p<0.001).

Quantitative assessment of eye movements during passage reading were highly informative of ataxia severity, were sensitive to disease progression, and enabled detection of subclinical signs. These properties support the inclusion of video-oculography-based measures of reading in natural history studies and clinical trials. Furthermore, this study demonstrates the feasibility of integration of oculomotor assessments in clinical workflows.

Abstract Figure
Tau Burden is Best Captured by Magnitude and Extent: Tau-MaX as a Measure of Global Tau
Authors: Brown Christopher A. , Das Sandhitsu R. , Cousins Katheryn A.Q. , Tropea Thomas F. , Plotkin Alice-Chen , Detre John A. , Yushkevich Paul A. , McMillan Corey T. , Lee Edward B. , Shaw Leslie M. , Nasrallah Ilya M. ,   the Alzheimer’s Disease Neuroimaging Initiative, Wolk David A.
Published: January 2025

Tau exhibits change in both spatial extent and density of pathology along the Alzheimer’s disease (AD) spectrum with each aspect contributing to the overall burden of pathological tau. Nevertheless, studies using Tau PET have measured either magnitude using standardized uptake value ratios (SUVRs) or extent using number of Tau+ regions. We hypothesized that combining these two dimensions into a single measure of Magnitude and eXtent, Tau-MaX, would provide improved quantification of global tau burden as well as allowing for a region-agnostic measure of global tau burden that does not require a pre-specified region of interest (ROI) or meta-ROI. To test this hypothesis, we analyzed18F-flortaucipir PET scans from local and national consortium data (n=1077 participants total) and used Gaussian-mixture models for data from 64 brain regions, to define both tau positivity and magnitude. We examined cross-sectional and longitudinal change in Tau-MaX across the Alzheimer’s disease (AD) spectrum and compared the association of Tau-MaX, magnitude, and extent with plasma p-tau217and global cognition. We also compared Tau-MaX using a global, region-agnostic approach to temporal lobe or Braak stage meta-ROIs. Whereas separate assessments of extent and magnitude across the disease spectrum found earlier increases in Tau spatial extent and later increases in magnitude, Tau-MaX was able to dynamically capture this shift demonstrating a stronger association with extent in the preclinical stage and a stronger association with magnitude in clinical stages. Global Tau-MaX differed between disease stages cross-sectionally and changed over time in all stages of disease. Further, Tau-MaX significantly improved associations with plasma p-tau217and global cognition compared to magnitude or extent alone. Finally, global measures of Tau-MaX performed similarly to meta-ROI measures of Tau-MaX. Together, these findings indicate that combining magnitude and extent provides a robust measure of global tau burden that changes throughout the disease course and is associated with blood-based biomarkers and cognition. This measure may be of particular use for disease staging, as well as serving as an outcome measure to monitor response to therapeutic intervention.
Expression of clock genes tracks daily and tidal time in brains of intertidal crustaceansEurydice pulchraandParhyale hawaiensis
Authors: Oliphant A. , Sia C.Y. , Kyriacou C.P. , Wilcockson D.C. , Hastings M.H.
Published: January 2025

Intertidal organisms, such as the crustaceansEurydice pulchraandParhyale hawaiensis, express daily and tidal rhythms of physiology and behaviour to adapt to their temporally complex environments. Although the molecular-genetic basis of the circadian clocks driving daily rhythms in terrestrial animals is well understood, the nature and mechanism of the circatidal clocks driving tidal rhythms remain a mystery. Usingin situhybridisation, we identified discrete clusters of ∼60 putative “clock” cells co-expressing canonical circadian clock genes with comparable distributions across the protocerebrum ofE. pulchraandP. hawaiensisbrains. In tidally rhythmic, field-collectedE. pulchrasampled under a light:dark (LD) cycle, the expression ofperiod(per) andcryptochrome 2(cry2) exhibited daily rhythms in particular cell groups (e.g., medioposterior cells) whereastimeless(tim) showed 12-hour rhythms in others (e.g., medial cells). In tidally rhythmic laboratory-rearedP. hawaiensis, previously entrained to 12.4-hour cycles of agitation under LD and sampled under continuous darkness, several cell groups (e.g., medioposterior cells) exhibited circadian expression ofperandcry2. In contrast, dorsal-lateral cells in the protocerebrum exhibited robust ∼12-hour, i.e., circatidal, rhythms ofperandcry2, phased to the prior tidal agitation but not the prior LD. InP. hawaiensisexhibiting daily behaviour under LD without tidal agitation, robust daily rhythms ofperandcry2expression were evident in medioposterior and other cells whereas expression in dorsal-lateral cells was not rhythmic, underlining their intrinsic tidal periodicity. These results implicate canonical circadian mechanisms in circatidal time-keeping and reveal conserved brain networks as potential neural substrates for the generation of interactive daily and tidal rhythms appropriate to intertidal habitats.
Analysis of potential mechanisms of non-carbapenemase mediated carbapenem resistance inAcinetobacter baumannii
Authors: Höfken Lisa-Marie , Gatermann Sören G. , Pfennigwerth Niels
Published: January 2025

Objectives

Acinetobacter baumanniiis a Gram-negative nosocomial pathogen that plays an important role in the context of bacterial multidrug-resistance. Increasing resistance to carbapenems in particular is of high therapeutic relevance, as in this case only a few antibiotics remain for treatment. The mechanisms of carbapenem resistance inA. baumanniiare mainly based upon carbapenemases and the mechanisms such as porin loss, efflux pumps and altered PBPs have been poorly studied to date.

Methods

TheA. baumanniireference strain ATCC 17978 was artificially mutated by selection pressure with increasing meropenem concentrations until carbapenem resistance was achieved. Growth analyses were carried out with the mutants and MICs for relevant antibiotics were determined. In addition, the mutants were whole genome sequenced, and the sequences were compared with the wild type. As various mutagenesis attempts for targeted construction of these respective mutants were unfortunately not successful, the strain collection of the NRC was screened for isolates that showed carbapenem resistance without a detectable carbapenemase. These isolates were sequenced and analysed for abnormalities in PBPs and porins in comparison to the sequence of the reference strain ATCC 17978 and were compared to other strains that possessed a carbapenemase.

Results

In three of the resulting ATCC 17978 mutants, a mutation of PBP2 was observed (W366L). Theses mutants were carbapenem resistant and were not affected by avibactam in contrast to the wild type ATCC 17978. Growth experiments indicated a fitness loss compared to the wild type.

As W366L was not found in the clinical isolates, we looked for other abnormalities in various genes associated with carbapenem resistance. Mutations were primarily found in the PBPs, with a mutation in PBP3 (A515V) occurring particularly often.

Conclusion

The results of this work support the prevailing thesis that PBP mutations inA. baumanniican lead to carbapenem resistance. Since there are hardly any studies on this hypothesis and for the most part only using outdated methods, these results are of particular relevance and further studies on this topic are recommended.
A common neuronal basis for Pavlovian and instrumental learning in amygdala circuits
Authors: Riffault Coline , Bitterman Yael , Müller Sigrid , Lüthi Andreas , Courtin Julien
Published: January 2025

Reward-predictive Pavlovian cues can selectively invigorate instrumental behaviors. Accumulating evidence pinpoints the basolateral amygdala (BLA) as a key brain structure to assign outcome-specific motivational significance to Pavlovian cues or Instrumental actions. However, whether neuronal representations of Pavlovian and Instrumental learnings are processed in different BLA circuits and how the resulting memories interact is unknown. Here, we used calcium imaging and optogenetic manipulation of the BLA neurons in mice that acquired and expressed Pavlovian and Instrumental behaviors in a multi-phase behavioral task called specific Pavlovian to Instrumental Transfer (sPIT). We first confirmed that Pavlovian cues selectively invigorate instrumental actions and showed that this effect, referred as the sPIT effect, depends on BLA activity. Then, by tracking the activity of single BLA neurons across days, we found that BLA neurons integrate common reward-anticipation information relevant for Pavlovian and instrumental learning. Interestingly, this reward-anticipation information re-emerged during subsequent memory transfer and covaried with sPIT effect. These findings reveal that the BLA encodes an outcome-specific motivational state that generalizes across Pavlovian and instrumental behaviors to promote and guide reward-seeking behavior.
Chloroform release from ageing cells andDrosophilaDJ-1 mutants
Authors: Issitt Theo , Johnston Timothy , Ugbode Chris , Grumulaityte Juste , Harmens Amy , Brackenbury William J , Sweeney Sean T , Redeker Kelly R
Published: January 2025

Volatile Organic Compounds (VOCs) offer potential for non-invasive diagnosis as biomarkers of disease and metabolism. In complex biological matrices, such as breath however, identifying useful biomarkers from hundreds, or even thousands of VOCs can be challenging. Models of disease, such as cellular or animal models, offer a means to elucidate VOC metabolisms, for accurate targeted studies in patient samples. Neurodegenerative conditions, such as parkinsons have been associated with changed VOCs, offering a potential for early diagnostics and interventions improving treatments and outcomes for patients. Here, three separate models including; human HEK-293t cells, isolated primary rat glial cells,Drosophilaflies (wild type and a mutant of the parkinson’s associated gene, DJ-1) were grown for an extended period and levels of the VOC chloroform (CHCl3) investigated using custom static headspace sampling chambers. Samples were analysed using targeted gas chromatography mass spectroscopy over time to generate metabolic flux values and chloroform shown to dramatically increase in all models as they aged. HEK-293t cells revealed a 60-fold increase after 10 weeks, glial cells revealed a 10-fold increase after 3 to 4 weeks and DJ-1 mutant flies revealed significant increases compared to control flies at 4 weeks. These results, taken together, indicate that chloroform release is related to ageing in these models and may provide a target for neurodegenerative studies moving forward. We present here the first evidence of chloroform being actively produced by human and rat cells and the first observation of volatile metabolisms inDrosophila.
Two Transport Routes for Fetuin-A-based Mineral Complexes in Osteogenic Matrix Mineralization
Authors: Schaart Judith M. , Rutten Luco , To Shaina V. , Shah Alisha A. , Martens Martijn , Macías-Sánchez Elena , Jahnen-Dechent Willi , Sommerdijk Nico , Akiva Anat
Published: January 2025

Fetuin-A is an abundant serum glycoprotein that prevents ectopic calcification. It has a high binding capacity for calcium phosphate and forms calciprotein monomers (CPM) and particles (CPP) upon binding. While it is also an abundant non-collagenous protein in bone, it’s role in bone matrix mineralization remains unclear. Using DLS and liquid-phase TEM, we identified a two-phase assembly process of primary CPPs, in which small and transient particles (tCPPs) are formed initially, after which larger, stable CPPs form. Using cell-free and osteoblast-based mineralization experiments, we found that CPMs and tCPPs can directly mineralize collagen fibrils, while CPPs are only a suitable mineral source after endocytosis and processing by matrix-producing osteoblasts. This indicates the existence of two potential transport routes for Fetuin-A/mineral complexes during bone matrix formation.
Deciphering Brain Organoids Heterogeneity by Identifying Key Quality Determinants
Authors: Kachkin Daniil , Zagha Naime , Boerstler Tom , Furlanetto Federica , Nayebzade Negar , Zappia Luke , Boisvert Michelle , Farrell Michaela , Ploetz Sonja , Regensburger Martin , Günther Claudia , Winkler Juergen , Gupta Pooja , Theis Fabian , Karow Marisa , Falk Sven , Winner Beate , Krach Florian
Published: January 2025

Brain organoids derived from human pluripotent stem cells (hPSCs) hold immense potential for modeling neurodevelopmental processes and disorders. However, their experimental variability and undefined organoid selection criteria for analysis hinder reproducibility. As part of the Bavarian ForInter consortium, we generated 72 brain organoids from distinct hPSC lines. We conducted a comprehensive analysis of their morphological and cellular characteristics at an early stage of their development. In our assessment, the Feret diameter emerged as a reliable, single parameter that characterizes brain organoid quality. Transcriptomic analysis further confirmed the reliability of this marker and identified a negative impact of mesenchymal cells on the abundance of organoid formation. High-quality organoids consistently displayed a lower mesenchymal cell presence. These findings offer a framework for enhancing brain organoid standardization and reproducibility, underscoring the need for morphological quality controls and the consideration of mesenchymal cell influence on organoid-based modeling.

Graphical Abstract
Combinatorial phosphorylation on CTD of RNA polymerase II selectively controls transcription and export of protein-coding mRNAs
Authors: Panina Svetlana B. , Irani Seema , Hardtke Haley A. , Stephenson Renee , Floyd Brendan M. , Moreno Rosamaria Y. , Marcotte Edward M. , Zhang Qian , Zhang Y. Jessie
Published: January 2025

C-terminal domain (CTD) of RNA polymerase II is crucial for recruiting transcription regulators via specific post-translational modifications (PTM), especially phosphorylation. The hypothesis of combination of PTMs, or ‘CTD code’, that can allow precise and dynamic recruitment of transcription machinery is highly attractive, yet the experimental evidence to support this hypothesis has been scarce. Here, despite lacking specific antibodies for combinatorial CTD phosphorylation, we developed an innovative approach that detects double phosphorylation patterns on the CTD in a whole-genomic fashion by leveraging the antibody masking effect with selectively removing the flanking interference. Using this method, we detected pT4pS5 double phosphosites occurring exclusively during the transcription of protein-coding genes. Furthermore, we showed that pT4pS5 marks recruit the Transcription and Export complex (TREX), which specifically facilitates mRNA processing and nucleocytoplasmic export of protein-coding mRNAs. The recruitment of TREX by pT4pS5 phosphosites is particularly important for the processing of lengthy neurogenesis-related genes. Our results provide experimental support for the notion that CTD coding system can function combinatorially and in a gene-specific manner, which encodes an exact information about the transcription of specific gene clusters. This method can be broadly applied to map all combinatorial PTM patterns on RNA polymerase II, paving the way for a deeper understanding of gene-specific transcription regulation at the molecular level.
Functional characterization of eicosanoid signaling inDrosophiladevelopment
Authors: Fujinaga Daiki , Nolan Cebrina , Yamanaka Naoki
Published: January 2025

20-carbon fatty acid-derived eicosanoids are versatile signaling oxylipins in mammals. In particular, a group of eicosanoids termed prostanoids are involved in multiple physiological processes, such as reproduction and immune responses. Although some eicosanoids such as prostaglandin E2 (PGE2) have been detected in some insect species, molecular mechanisms of eicosanoid synthesis and signal transduction in insects have been poorly investigated. Our phylogenetic analysis indicated that, in clear contrast to the presence of numerous receptors for oxylipins and other lipid mediators in humans, theDrosophilagenome only possesses a single ortholog of such receptors, which is homologous to human prostanoid receptors. This G protein-coupled receptor, named Prostaglandin Receptor or PGR, is activated by PGE2 and its isomer PGD2 inDrosophilaS2 cells.PGRmutant flies die as pharate adults with insufficient tracheal development, which can be rescued by supplying high oxygen. Consistent with this, through a comprehensive mutagenesis approach, we identified aDrosophilaPGE synthase whose mutants show similar pharate adult lethality with hypoxia responses.Drosophilathus has a highly simplified eicosanoid signaling pathway as compared to humans, and it may provide an ideal model system for investigating evolutionarily conserved aspects of eicosanoid signaling.

Author Summary

There are numerous bioactive lipids that control animal physiology, and some of them are commonly observed in both humans and insects. Well-studied insects such as fruit flies can therefore be an excellent gateway to learn about lipid molecules that have common functions in various animal species. In this study, we analyzed the fruit fly genome to look for genes that encode sensors (or receptors) for such lipid molecules called lipid mediators and found that the fruit fly only has one such receptor, as compared to ∼50 receptors in humans. Interestingly, the fly receptor we found was similar to human receptors for lipid molecules called prostanoids. Our work on the fruit fly prostanoid receptor further revealed that it is important for development of the fly respiratory system, and we showed that flies can also synthesize prostanoids in their body just like humans. Prostanoids are clinically important due to their pro-inflammatory functions, and some widely used drugs such as ibuprofen target enzymes that synthesize prostanoids. Our study on fruit fly prostanoids therefore provides a solid basis for using this simple organism to reveal common prostanoid functions in animals, which may provide important insights into animal health in general.
In vitro reconstitution defines the mechanistic basis of HSET motor activity regulation by IntraFlagellar Transport proteins
Authors: Guesdon Audrey , Simon Valérie , Van Dijk Juliette , Delaval Bénédicte , Vitre Benjamin
Published: January 2025

HSET is a mitotic kinesin essential for centrosome clustering in cells harboring supernumerary centrosomes. Workin cellulorevealed that IntraFlagellar Transport proteins (IFT) interact with the kinesin HSET to promote efficient extra centrosome clustering and subsequent cancer cell proliferation. However, whether and how IFT proteins regulate HSET activity is unknown. Using a reconstitutedin vitrosystem combining purified HSET and IFT proteins coupled to TIRF microscopy approaches, we identified a minimal subcomplex made of IFT52/IFT70 directly binding to HSET. We demonstrate that this binding induces HSET oligomerization allowing its activation and the formation of processive HSET complexes. We also show that HSET activation by IFT proteins accounts for an increased ability to slide microtubules and to organize dynamic microtubule networksin vitro. Overall, this work shows that IFT proteins can directly activate a mitotic kinesin and provides mechanistic explanation for the contribution of IFT proteins to efficient centrosome clustering.
Frontoparietal activity related to neuropsychological assessment of working memory
Authors: Jurva August , Singh Balbir , Qian Helen , Wang Zhengyang , Jacobs Monica L. , Dhima Kaltra , Englot Dario J. , Roberson Shawniqua Williams , Bick Sarah K. , Constantinidis Christos
Published: January 2025

Executive functions, including working memory, are typically assessed clinically with neuropsychological instruments. In contrast, computerized tasks are used to test these cognitive functions in laboratory human and animal studies. Little is known of how neural activity captured by laboratory tasks relates to ability measured by clinical instruments and, by extension, clinical diagnoses of pathological conditions. We therefore sought to determine what aspects of neural activity elicited in laboratory tasks are predictive of performance in neuropsychological instruments. We recorded neural activity from intracranial electrodes implanted in human epilepsy patients as they performed laboratory working memory tasks. These patients had completed neuropsychological instruments preoperatively, including the Weschler Adult Intelligent Scale and the Wisconsin Card Sorting test. Our results revealed that increased high-gamma (70-150 Hz) power in the prefrontal and parietal cortex after presentation of visual stimuli to be remembered was indicative of lower performance in the neuropsychological tasks. On the other hand, we observed a positive correlation between high-frequency power amplitude in the delay period of the laboratory tasks and neuropsychological performance. Our results demonstrate how neural activity around task events relates to executive function and may be associated with clinical diagnosis of specific cognitive deficits.
Unveiling the Evolution of Antimicrobial Peptides in Gut Microbes via Foundation Model-Powered Framework
Authors: Li Wenhui , Huang Baicheng , Guo Menghao , Zeng Zihan , Cai Tao , Feng Linqing , Zhang Xinpeng , Guo Ling , Jiang Xianyue , Yin Yanbin , Wang Ercheng , Huang Xingxu , Zheng Jinfang
Published: January 2025

Antimicrobial resistance poses a growing threat to public health, emphasizing the urgent need for novel therapeutic strategies. Antimicrobial peptides (AMPs), short peptide sequences with diverse mechanisms of action, offer a promising alternative due to their broad-spectrum activity against pathogens. Recent advances in protein language models (PLMs) have revolutionized protein structure prediction and functional annotation, highlighting their potential for AMP discovery and therapeutic development. In this context, we present AMP-SEMiner (Antimicrobial Peptide Structural Evolution Miner), an AI-driven framework designed to identify AMPs from metagenome-assembled genomes (MAGs). By integrating PLMs, structural clustering and evolutionary analysis into the framework, AMP-SEMiner can identify AMPs encoded by small open reading frames (smORFs) and encrypted peptides (EPs), significantly expanding the discovery space. Using this approach, we identified 1,670,600 AMP candidates from diverse habitats. Experimental validation of 29 candidates revealed antimicrobial activity in 18, with 13 surpassing antibiotics in effectiveness. Further analysis of AMPs from human gut microbiomes demonstrated both conserved and adaptive evolutionary strategies, ensuring their functional efficacy in the dynamic gut environment. These findings position AMP-SEMiner as a powerful tool for the discovery and characterization of novel AMPs, with significant potential to drive the development of new antimicrobial therapies.
Genomic insights into six clinical isolates ofStenotrophomonas maltophiliafrom Northern India
Authors: Gheewalla Nazneen , Jadhav Yuvraj , Jagannadham Jaisri , Tyagi Akansha , Budhiraja Sandeep , Tarai Bansidhar , Karve Shraddha
Published: January 2025

Stenotrophomonas maltophiliais a gram-negative opportunistic pathogen that causes respiratory, urinary and bloodstream infections. Due to rising prevalence of difficult to treatS. maltophiliainfections, it is considered as one of the important pathogens in many regions, including India. Despite its importance in public health, very few studies provide detailed characterization of the genomes of clinical isolates ofS. maltophilia. In this study, we sequence six isolates ofS. maltophiliafrom a tertiary healthcare centre in the Northern India. Along with the culture sensitivity, we report the genomic underpinnings of resistance and virulence in these isolates. In three out of six isolates, we identify a rare beta-lactamase genekbl-1that can confer resistance to variety of beta-lactam antibiotics. Though truncated in two isolates, an intact copy ofkbl-1is present in the third isolate. This intact copy ofkbl-1is flanked by insertion elements that are commonly found in several pathogenic species indicating high potential for horizontal gene transfer. To the best of our knowledge, this is a first report ofkbl-1inS. maltophiliafrom India.

Importance

Antimicrobial resistance (AMR) is one of the biggest global public health challenges. Tackling AMR gets complicated as diverse pathogenic species are involved and resistance is manifested against several different kinds of antibiotics. Genomic surveillance of the resistant pathogens is a key to fight this global threat and needs to extend to important emerging pathogens as well. Here we report genomic sequences and associated characteristics of sixStenotrophomonas maltophiliaisolates from Northern India. Along with several resistance and virulence genes we also discover a rare beta-lactamase,blaKBL-1, gene with a high potential of transfer to other species.blaKBL-1beta-lactamase confers resistance to several beta-lactam antibiotics like ampicillin, amoxicillin, penicillin G, piperacillin, ceftazidime and cefozopran. This is the first report of the presences of this beta-lactamase from India.
Prenatal and early childhood exposure to antibiotics or gastric acid inhibitors and increased risk of epilepsy: A nationwide population-based study
Authors: Gudnadottir Unnur , Wickström Ronny , Gunnerbeck Anna , Prast-Nielsen Stefanie , Brusselaers Nele
Published: January 2025

Over 10 million children in the world have epilepsy, with unknown root cause in approximately half of cases. The gut microbiome has been associated with various neurological disorders, and certain drugs greatly disturb the microbiome. Our aim was to study the association of prenatal and childhood exposure (before the age of two) of antibiotics, proton pump inhibitors and histamine-2 receptor antagonists, and the risk of childhood epilepsy. Using population-based registers, we included all live singleton births in Sweden from 2006-2017. Exposure was considered prescription(s) to antibiotics, proton pump inhibitors or H2-receptor antagonists (separately) during pregnancy or the first two years of life.

Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals.

In total 708,903 mother-child dyads were included, and 0.5% of children were diagnosed with epilepsy. Average follow-up time was 3.8 years (IQR 1-6). Prenatal exposure to antibiotics (aHR 1.09, 95%CI 1.01-1.18) and proton pump inhibitors (aHR 1.38, 95%CI 1.17-1.65) were associated with an increased risk of epilepsy. Additionally, exposure to antibiotics (1.13, 95%CI 1.04-1.23), PPIs (3.82, 95%CI 2.83-5.16) and H2RAs (1.65, 95%CI 1.03-2.64) before the age of two was associated with an increased risk of epilepsy after the age of two.

To conclude, our results support the hypothesis that microbiome modulating drugs are associated with an increased risk of epilepsy. This association needs to be further validated in other studies, ideally including the indications for drug use. Our results hopefully contribute to further studies or better prevention of childhood epilepsy.
Optimizing bioconvective heat transfer with MHD Eyring–Powell nanofluids containing motile microorganisms with viscosity variability and porous media in ciliated microchannels
Authors: Mehboob Junaid , Ellahi R. , Sait Sadiq M. , Akbar Noreen Sher
Published: January 2025

Purpose

This paper aims to optimize bioconvective heat transfer for magnetohydrodynamics Eyring–Powell nanofluids containing motile microorganisms with variable viscosity and porous media in ciliated microchannels.

Design/methodology/approach

The flow problem is first modeled in the two-dimensional frame and then simplified under low Reynolds number and long wavelength approximations. The numerical method is used to examine the impact of thermal radiation, temperature-dependent viscosity, mixed convection, magnetic fields, Ohmic heating and porous media for velocity, temperature, concentration and motile microorganisms. Graphical results are presented to observe the impact of physical parameters on pressure rise, pressure gradient and streamlines.

Findings

It is observed that the temperature of nanofluid decreases with higher values of the viscosity parameter. It is absolutely in accordance with the physical expectation as the radiation parameter increases, the heat transfer rate at the boundary decreases. Nanoparticle concentration increases by increasing the values of bioconvection Rayleigh number. The density of motile microorganisms decreases when bioconvection Peclet number is increased. The velocity of the nanofluid decreases with higher value of Darcy number. With increase in the value of bioconvection parameter, the flow of nanofluid is increased.

Originality/value

The bioconvective peristaltic movement of magnetohydrodynamic nanofluid in ciliated media is proposed. The non-Newtonian behavior of the fluid is described by using an Eyring–Powell fluid model.
International business education experiences through temporary learning environments: evidence from Atlantic Canada
Authors: Kalafsky Ronald V. , Raymond Mark P.
Published: January 2025

Purpose

International environments introduce a number of learning-related barriers for students endeavoring to understand global business practices. One way in which these obstacles can be addressed is through participation in temporary learning environments (TLEs), such as trade fairs and similar events. This paper aims to examine how international trade missions (ITMs) – a type of short-term, study-abroad experience – were used as TLEs by students at an Atlantic Canada university as part of their EMBA curriculum to gain practical experience in international business environments.

Design/methodology/approach

This study explores the ways in which students benefitted from participation in the ITMs and resulting TLEs. Accordingly, an online survey that explored export-related issues and learning outcomes was administered to EMBA students who participated in this program to ascertain the ways in which these events furthered their educational experience and how the ITMs enabled them to perceive challenges and strategies related to international market expansion.

Findings

A survey of ITM participants revealed that students gained insights into firm-level barriers to internationalization in addition to a practical understanding of general challenges in international trade. At the same time, some observations suggested that more emphasis could be placed on pre-trip preparations and post-trip networking. The paper concludes with discussions on how short-term study abroad opportunities can serve as TLEs, in addition to proposing future ways in which the ITMs could provide even more experiences for the students.

Originality/value

The value-added from this paper is found in two ways. The first is to illustrate how ITMs can be a form of a TLE for students. The second, linked contribution, is to reinforce and to provide further evidence on how the TLEs – a short study-abroad opportunity – can be an environment in which students obtain valuable, hands-on international business experience.
Trends and hotspots in public food procurement: exploring planetary boundaries and human needs in an integrative literature review
Authors: Akim Erica Kushihara , Silva Diogo Aparecido Lopes , Faria Luiz Carlos de
Published: January 2025

Purpose

Using an Integrative Literature Review (ILR), this study aims to investigate the components defining the Safe and Just Operating Space (SJOS) within food systems and assess their applicability in decision-making for public food procurement (PFP).

Design/methodology/approach

Data concerning SJOS implementation in food systems and the criteria used in PFP were retrieved from the Web of Science and Scopus databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol.

Findings

The analysis of the literature highlights that climate change (n = 31; 17%) and water use (n = 29; 16%) are the primary focus areas regarding Planetary Boundaries (PB), followed the nitrogen cycle, land use, biodiversity loss and the phosphorus cycle. In PFP, key criteria linked to PB encompass climate change (n = 19; 7.2%), water use (n = 17; 6.44%) and chemical pollution (n = 17; 6.44%). The social and ethical dimensions underscore labour (n = 18; 6.82%), water (n = 17; 6.44%), income (n = 16; 6.06%) and energy (n = 16; 6.06%).

Research limitations/implications

Despite the strengths of this study, certain limitations should be acknowledged. Although the inclusion and exclusion criteria for the reviewed articles were clearly defined, it is possible that relevant literature was unintentionally excluded. Expanding the scope to include grey literature – such as government documents, reports, policy statements and statistical reports – could provide additional insights and broaden the scope of the findings. Moreover, the search was limited to the Web of Science and Scopus databases, which may have resulted in the omission of relevant studies, particularly those published in non-English languages or not indexed journals.

Practical implications

The identified procurement criteria can help public administrators develop guidelines and tools for food procurement that consider the SJOS.

Social implications

This paper offers an understanding of the connection between planetary processes and human well-being in the context of PFP.

Originality/value

This pioneering research lays the groundwork for future agendas in this field and encourages reflection on critical factors essential for selecting methods and standards applied in practical public procurement.
Understanding the influence of ride-sharing value on consumers’ continuance intention
Authors: Chen Hao , Zhou Xi
Published: January 2025

Purpose

This study aims to understand the mechanism by which the value of ride-sharing services influences consumers’ continuance intention.

Design/methodology/approach

The authors collected data from 484 Chinese ride-sharing respondents and analyzed them using partial least squares structural equation modeling.

Findings

The results show that hedonic value, social connection value and environmental value positively affect consumers’ cognitive fit and emotional fit, while utilitarian value has no significant effect on either cognitive fit or emotional fit. In addition, both cognitive fit and emotional fit significantly affect consumers’ satisfaction and continuance intention. Furthermore, satisfaction mediates the effects of cognitive and emotional fit on continuance intention.

Practical implications

Ride-sharing practitioners should have a clear understanding of all the value dimensions of ride-sharing services, which would subsequently increase customers’ continuance intention.

Originality/value

This study defines and divides the dimensions of ride-sharing value and demonstrates the significant impact of environmental value on the sustainability of ride-sharing services. This study extends fit theory by dividing it into two dimensions.
Pancreatic endometrioma in a post‐menopausal woman: A rare differential diagnosis for cystic lesions of the pancreas
Authors: Koçi Sara , Dinçer Hilmi Anıl , Arslan Alican , Kiki Zehranur , Sökmensüer Cenk , Doğrul Ahmet Bülent
Published: January 2025

Background

Although endometriosis is a relatively common condition affecting women, pancreatic endometriosis remains rare, with only a few cases reported in the literature. The primary challenges this condition poses today are its inability to be diagnosed radiologically and the difficulty in distinguishing it from other cystic lesions of the pancreas preoperatively.

Methods

This report presents a case of a 53‐year‐old female patient with 3 months long left upper quadrant pain and no previous medical history. Imaging revealed an enlarging cyst in the tail of the pancreas, with findings suggestive of a mucinous neoplasm.

Results

The patient underwent a distal pancreatectomy and splenectomy. Histopathological analysis confirmed the presence of endometrial stroma.

Conclusions

Considering the possibility of pancreatic endometriosis may help avoid extensive surgery. However, as the definite diagnosis of endometriosis remains histopathological, surgical resection continues to be the treatment of choice if malignancy is suspected.
Long‐Term Real‐World Survival of Immunotherapy Compared to Chemotherapy for Metastatic Nonsmall Cell Lung Cancer: A Propensity Score‐Matched Analysis
Authors: Kim Kun , Sweeting Michael , Jönsson Linus , Wilking Nils
Published: January 2025

Background

The long‐term real‐world effect of immunotherapy (IO) is uncertain in metastatic nonsmall cell lung cancer (mNSCLC). This retrospective observational study aimed to describe treatment patterns following the introduction of IO, estimate real‐world treatment effects of IO compared to standard of care, and evaluate the impact of introduction of IO on a real‐world population, based on a large dataset of over 10 000 patients with several years of follow‐up.

Methods

Data from routine care of lung cancer patients were extracted from Flatiron Health including those who received either IO or platinum‐based doublet chemotherapy (PBDC) in the first line (1L), or either IO or chemotherapy (CT) in the second line (2L). Real‐world overall survival (rwOS) and real‐world time to next therapy (rwTTNT) were estimated using Cox regression. Flexible parametric models, relaxing proportional hazard assumptions, were used to evaluate long‐term IO effects.

Results

After 1:1 nearest neighbor matching among 16 754 1L and 6548 2L patients, the hazard ratio (HR) was 0.942 (95% CI, 0.902–0.984) in 1L and 0.853 (95% CI, 0.795–0.915) in 2L. Adjusting for crossover effects, HR was 0.887 in 1L and 0.775 in 2L. Over the 7‐year follow‐up, the mean rwOS benefit was 3.2 months for 1L and 2.7 months for 2L. IO significantly delayed rwTTNT in both 1L and 2L. The IO effects increased and persisted over time, with uncertainty in the time‐varying HR estimate.

Conclusion

IO improves survival in patients with mNSCLC, though the effect size is smaller than in trials and long‐term survival estimates are uncertain.
Intratumor Heterogeneity Predicts Prognosis in Lepidic Predominant Lung Adenocarcinoma
Authors: Niedermaier Benedikt , Allgäuer Michael , Muley Thomas , Schneider Marc A. , Eichhorn Martin E. , Winter Hauke , Klotz Laura V.
Published: January 2025

Objective

Among the different subtypes of invasive lung adenocarcinoma, lepidic predominant adenocarcinoma (LPA) has been recognized as the lowest‐risk subtype with good prognosis. The aim of this study is to provide insight into the heterogeneity within LPA tumors and to better understand the influence of other sub‐histologies on survival outcome.

Methods

Overall, 75 consecutive patients with LPA in pathologic stage I (TNM 8th edition) who underwent resection between 2010 and 2022 were included into this retrospective, single center analysis. The proportions of different growth patterns were reported in 5% increments according to the WHO classification.

Results

All tumors exhibited a predominantly lepidic growth pattern (median proportion 70%, IQR 60%–85%). The invasive component included acinar (n = 66, 88%), papillary (n = 41, 55%), micropapillary (n = 14, 19%), and solid growth patterns (n = 4, 5%), with most tumors exhibiting more than one invasive growth pattern. The presence of high‐risk growth, that is, micropapillary and solid, was associated with higher T stage (r = 0.423, p = 0.0002). A classification of patients as lepidic/high‐risk or lepidic/low‐risk based on the presence of micropapillary and solid growth patterns resulted in a significantly worse disease‐free survival (p = 0.0169, 5‐year DFS: lepidic/high‐risk 73% vs. lepidic/low‐risk: 95%) for the lepidic/high‐risk group, while the groups did not differ in age, gender, smoking status, or extent of resection.

Conclusion

Patients with stage I LPA exhibit considerable intratumor heterogeneity regarding growth patterns, which can be used for prognostic stratification. The occurrence of micropapillary and solid growth patterns in LPA is associated with poorer disease‐free survival.
Using causal diagrams and superpopulation models to correct geographic biases in biodiversity monitoring data
Authors: Boyd Robin J. , Botham Marc , Dennis Emily , Fox Richard , Harrower Collin , Middlebrook Ian , Roy David B. , Pescott Oliver L.
Published: January 2025

Biodiversity monitoring schemes periodically measure species' abundances and distributions at a sample of sites to understand how they have changed over time. Often, the aim is to infer change in an average sense across some wider landscape. Inference to the wider landscape is simple if the species' abundances and distributions are similar at sampled to non‐sampled locations. Otherwise, the data are geographically biased, and some form of correction is desirable.

We combine causal diagrams with ‘superpopulation models’ to correct time‐varying geographic biases in biodiversity monitoring data. For a given time‐period, expert‐derived causal diagrams are used to deduce the set of variables that explain the geographic bias, and superpopulation models adjust for these variables to produce a corrected estimate of a landscape‐wide mean of for example abundance or occupancy. Estimating a time trend in the variable of interest is achieved by fitting models for multiple time‐periods and, if the drivers of bias are suspected to change over time, by constructing per period causal diagrams. We test the approach using simulated data then apply it to real data from the UK Butterfly Monitoring Scheme (UKBMS).

If the variables that explain the geographic bias are known and measured without error, our method is unbiased. Introducing measurement error reduces the method's efficacy, but it is still an improvement on using the sample mean. When applied to data from the UKBMS, the approach gives different results to the scheme's current method, which assumes no geographic bias.

Where the goal is to estimate change in some variable of interest at the landscape level (e.g. biodiversity indicators), models that do not adjust for geographic bias implicitly assume it does not exist. Our approach makes the weaker assumption that there is no geographic bias conditional on the adjustment variables, so it should yield more accurate estimates of time trends in many circumstances. The method does require assumptions about the drivers of bias, but these are codified explicitly in the causal diagrams. Operationalising our approach should be less costly than full probability sampling, which would be needed to satisfy the assumptions of conventional approaches.
Farming the North: Cycles of Extraction and Dispossession
Authors: Rotz Sarah , Rück Daniel , LeBlanc Joseph
Published: January 2025

This paper examines recent initiatives to expand farming in Northern Ontario, Canada, situating these within the historical context of settler colonial agriculture. We ask: how do contemporary efforts in agricultural expansion differ from, or replicate, earlier forms of land acquisition? Focusing on land assembly, we explore how land consolidation, privatisation, and conversion meet agricultural and economic objectives under contemporary colonial capitalism. We consider whether agricultural expansion reinforces narratives that valorise settler agriculture and/or perpetuates patterns of dispossession. Through privatisation and competitive marketisation of “underutilised” lands, agricultural expansion may reconfigure land ownership in ways that serve capital interests and, primarily, settler agricultural entities. This case highlights the role of agricultural development and the interdependence of corporate and state actors in extending financialised land economies, potentially undermining Indigenous food sovereignty, jurisdiction, and autonomy.
Understanding the Importance of the Small Artery Media–Lumen Ratio: Past and Present
Authors: Aalkjaer Christian
Published: January 2025

The media–lumen diameter ratio of small arteries is increased in hypertension, diabetes and obesity. It is likely that both shear stress on the endothelial cells, transmural pressure and smooth muscle cell tone are important for the altered vascular structure. However, the precise interaction and importance of these factors are incompletely understood. At the molecular level transglutaminases, metalloproteinases, integrins, NO and several other factors have been suggested to be important, but our understanding of how the many factors together control vascular structure is surprisingly limited. The media–lumen diameter ratio of the small arteries has prognostic value, which is independent of the classical risk factors for cardiovascular disease. Importantly this is also the case in patients treated pharmacologically for high blood pressure. It is therefore relevant to consider small artery structure as a potential target in relation to prevention of cardiovascular disease.