bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world epilepsy monitoring with ultra long-term subcutaneous EEG: a 15-month prospective study
Authors: Viana Pedro F. , Duun-Henriksen Jonas , Biondi Andrea , Winston Joel S. , Freestone Dean R. , Schulze-Bonhage Andreas , Brinkmann Benjamin H. , Richardson Mark P. 
Published: November 2024

AbstractObjectiveNovel subcutaneous electroencephalography (sqEEG) systems enable prolonged, near-continuous cerebral monitoring in real-world conditions. Nevertheless, the feasibility, acceptability and overall clinical utility of these systems remains unclear. We report on the longest observational study using ultra long-term sqEEG to date.MethodsWe conducted a 15-month prospective, observational study including ten adult people with treatment-resistant epilepsy. After device implantation, patients were asked to record sqEEG, to use an electronic seizure diary and to complete acceptability and usability questionnaires. sqEEG seizures were annotated visually, aided by automated detection. Seizure clustering was assessed via Fano Factor analysis and seizure periodicity at multiple timescales was investigated through circular statistics.ResultsOver a median duration of 438 days, ten patients recorded a median 18.8 hours/day, totalling 71,984 hours of real-world sqEEG data. Adherence and acceptability remained high throughout the study. While 754 sqEEG seizures were recorded across patients, over half (52%) of these were not reported in the patient diary. Of the 140 (27%) diary reports not associated with an identifiable sqEEG seizure, the majority (68%) were reported as seizures with preserved awareness. The sqEEG to diary F1 agreement score was highly variable, ranging from 0.06 to 0.97. Patient-specific patterns of seizure clustering and seizure periodicity were observed at multiple (circadian and multidien) timescales.InterpretationWe demonstrate feasibility and high acceptability of ultra long-term (months-years) sqEEG monitoring. These systems help provide real-world, more objective seizure counting compared to patient diaries. It is possible to monitor individual temporal fluctuations of seizure occurrence, including seizure cycles.Summary for Social Media if Published[I do not have a X/Twitter handle]People with epilepsy may suffer from severe injuries or sudden death due to uncontrolled seizures. Many seizures remain unnoticed by people and unreported to doctors, despite these potentially catastrophic consequences. There is an urgent need to detect seizures more objectively. Our study used a novel device placed under the skin to monitor brainwave activity continuously, at home, for many months, in people with treatment-resistant epilepsy. By monitoring epilepsy from home, we detected many seizures unreported by patients, and we also found predictable patterns (cycles) of seizure occurrence over time. In the future, this type of monitoring could revolutionize epilepsy care, by improving safety, treatment management and reducing uncertainty in patients’ daily lives.
Bias in control selection associated with the use of rapid tests in influenza vaccine effectiveness studies
Authors: Poukka Eero , Murphy Caitriona , Mak Loretta , Cheng Samuel M. S. , Peiris Malik , Tsang Tim K. , Sullivan Sheena G. , Cowling Benjamin J. 
Published: November 2024

AbstractIn test-negative design studies that use rapid tests to estimate influenza vaccine effectiveness (VE) a common concern is case/control misclassification due to imperfect test sensitivity and specificity. However, an imperfect test can also fail to exclude from the control group people that do not represent the source population, including people infected with other influenza types or other vaccine-preventable respiratory viruses for which vaccination status is correlated. We investigated these biases by comparing the effectiveness of seasonal 2023/24 influenza vaccination against influenza A and B based on PCR versus rapid test results, excluding controls who tested positive for SARS-CoV-2 or the other type of influenza. By PCR, VE against influenza A was 49% (95%CI 26–65%) after exclusion of PCR-confirmed influenza B and SARS-CoV-2 controls. Corresponding VE against influenza B was 65% (95%CI 35–81%). VE estimated by adjusting for COVID-19 vaccination status yielded similar estimates to the scenario that excluded SARS-CoV-2-positive controls. When case/control status and exclusions from test-negative controls were determined by rapid test, VE was reduced by 5–15 percentage points. Bias correction methods were able to reduce these discrepancies. When estimating VE from a test-negative study using rapid test results, methods to correct misclassification bias are recommended.
CB1 and CB2 receptors differentially modulate the cognitive impact of maternal immune activation and perinatal cannabinoid exposure
Authors: Chen Han-Ting , Mackie Ken 
Published: November 2024

AbstractMaternal immune activation (MIA) commonly arises in response to an infection during pregnancy. MIA elevates cytokine levels, triggering an inflammatory cascade, which may be detrimental to the developing nervous system. Similarly, cannabis use and exposure of the fetus to cannabinoids during pregnancy (PCE) may elicit neuroinflammation and lead to detrimental behavioral outcomes. This is particularly concerning as there has been a notable rise in cannabis use during pregnancy. This study endeavors to examine the interaction between MIA and PCE and elucidate the role of CB1 and CB2 receptors in MIA and PCE outcomes. To this end, we compared the impact of MIA, PCE and MIA+PCE in wildtype, CB1, and CB2 cannabinoid receptor knockout mice of both sexes. PCE was modeled by daily 3 mg/kg THC administration from gestational day 5 (GD5) to postnatal day 10. MIA was modeled by intravenous Poly (I:C) injection at GD16.5. Subsequently, we assessed emotional and cognitive behaviors of adult offspring. Adult male offspring of dams exposed to PCE or MIA were impaired in novel object recognition and the delayed alternation working memory tasks. Interestingly, these behavioral impairments were absent when MIA and PCE were combined. Cannabinoid receptor knockout studies found that CB1 receptors mediated behavioral deficits after PCE. In contrast CB2 receptors were necessary for full expression of MIA-induced behavioral impairments. Although females showed more modest behavioral changes after MIA or PCE, CB1 receptors were required for the PCE deficit and CB2 receptors were required for the MIA deficit also in females. Notably, lack of CB2 receptors in males prevented the “protection” following combined MIA + PCE, while CB1 knockout mice remained protected. Taken together, these results suggest a complex interplay between PCE, MIA and CB1 and CB2 cannabinoid receptors.HighlightsBoth PCE and MIA impair cognitive behaviors.Combined PCE and MIA did not affect the cognitive behaviors examined.CB1 receptors are required for deficits after prenatal cannabis exposure.CB2 receptors are required for deficits after maternal immune activation.CB2 receptors are necessary for protection from deficits by combined PCE and MIA.
Assessing the helical stability of polyXYs at the boundaries of Intrinsically Disordered Regions with MD simulations
Authors: Gonçalves-Kulik Mariane , Baptista Luis A. , Schmid Friederike , Andrade-Navarro Miguel A. 
Published: November 2024

AbstractIntrinsically disordered regions (IDRs) in proteins lack stable structure. By carrying many hydrophilic and charged residues, it prevents them from forming globular domains and contributes to their flexibility and accessibility. Naturally, regions with reduced amino acid composition (low complexity regions; LCRs) occur within IDRs. Disorder and low complexity in protein sequences are linked to various biological functions including phase separation, regulation, and molecular interactions, and mutations in these regions can contribute to several diseases including cancer. Understanding these biological properties requires examination of the structural properties of IDRs and the LCRs within, but their inherently dynamic nature requires specific approaches combining sequence analyses, structure predictions and molecular dynamics (MD) simulations. Here, we leverage our previous work where we identified that some types of LCRs combining two residues (polyXY) are frequent within IDRs and confer them with propensity to form helical conformation. We identify a significant accumulation of such polyXYs at the ends of IDRs following alpha-helices that start outside the IDR and may extend through the polyXY into the IDR, particularly from the N-terminal end of the IDR. MD simulations support the dynamic nature of such helical conformations. Our results suggest a mechanism by which evolutionary emergence of LCRs at IDR ends could provide proteins with flexible regions for fold-upon-binding.
An animal model for autoinflammation with infantile enterocolitis
Authors: Wang Yuhang , Gao Joyce Z. , Gurung Prajwal , Short Sarah P. , Xiong Yiqin , Kang Zizhen 
Published: November 2024

AbstractInflammasomes, particularly NLRC4, play a crucial role in immune responses to intracellular bacterial infections. However, gain-of-function mutations of NLRC4 are linked to severe autoinflammatory diseases, including autoinflammation with infantile enterocolitis (AIFEC). Existing mouse models do not adequately replicate the chronic, unprovoked inflammation observed in AIFEC patients. In this study, we developed a loxP-flanked NLRC4 V341A knock-in (KI) mouse model. Our global NLRC4 V341A KI mice exhibited symptoms closely mirroring those of human AIFEC. These mice demonstrated severe infantile enterocolitis, characterized by heightened intestinal inflammation, compromised intestinal barrier integrity, disrupted gut epithelium, and severe diarrhea, with high mortality within 10 days postnatally. Additionally, they displayed systemic autoinflammation marked by elevated levels of IL-1β, IL-18, and IL-6, alongside cytopenia and hemophagocytosis. In contrast, adult NLRC4 conditional KI mice exhibited autoinflammation with only mild enterocolitis. Since AIFEC is characterized by life-threatening enterocolitis in infancy and recurrent severe autoinflammation throughout life, our conditional NLRC4 KI model effectively recapitulates the clinical features of human AIFEC. Moreover, the NLRC4 V341A-mediated monogenic infantile enterocolitis observed in our model resembles infantile-onset inflammatory bowel disease (IBD), positioning it as a valuable platform for research on very early-onset IBD.
VNC-Dist: A machine learning-based tool for quantification of neuronal positioning in the ventral nerve cord ofC. elegans
Authors: Saharkhiz Saber , Petite Mearhyn , Roenspies Tony , Perkins Theodore , Colavita Antonio 
Published: November 2024

AbstractThe ventral nerve cord (VNC) of newly hatchedC. eleganscontains 22 motoneurons organized into three distinct classes: DD, DA, and DB, that show stereotypical positioning and arrangement along its length. The VNC represents a genetically tractable model to investigate mechanisms involved in neuron sorting and positioning. However, accurately and efficiently mapping and quantifying all motoneuron positions within large datasets is a major challenge. Here, we introduce VNC-Dist, a semi-automated software toolbox designed to overcome the limitations of subjective motoneuron positioning analysis in microscopy. VNC-Dist uses an annotator for neuron localization and an automated contour-based method for measuring the relative distances of neurons along the VNC based on deep learning and numerical analysis. To demonstrate the robustness and versatility of VNC-Dist, we applied it to multiple genetic mutants known to disrupt neuron positioning in the VNC. This toolbox will enable the acquisition and analysis of large datasets on neuronal positioning, thereby advancing investigations into the cellular and molecular mechanisms that control neuron positioning and arrangement in the VNC.
Criterial Learning and Feedback Delay: Insights from Computational Models and Behavioral Experiments
Authors: Crossley Matthew J. , Pelzer Benjamin O. , Ashby F. Gregory 
Published: November 2024

AbstractThe notion of a response criterion is ubiquitous in psychology, yet its cognitive and neural underpinnings remain poorly understood. To address this shortcoming, three computational models that capture different hypotheses about criterial learning were developed and tested. The time-dependent drift model assumes the criterion is stored in working memory and that its value drifts over time. The delay-sensitive learning model assumes that the magnitude of criterial learning is temporally discounted by feedback delay. The reinforcement-learning model assumes that criterial learning emerges from stimulus-response association learning without an explicit representation of the criterion, with learning rate also temporally discounted by feedback delay. The performance of these models was investigated under varying feedback delay and intertrial interval (ITI) durations. The time-dependent drift model predicted that long ITIs and feedback delays both impair criterial learning. In contrast, the delay-sensitive and reinforcement-learning models predicted impairments only with feedback delays. Two behavioral experiments, which tested these predictions, showed that human criterial learning is impaired by delayed feedback but not by long ITIs. These results support the delay-sensitive and reinforcement-learning models, and suggest that even in tasks that appear to rely on explicit, rule-based reasoning, criterial learning may have strong associative underpinnings.
A Qualitative Exploration of the use Social Media for Learning by Emergency Medicine Doctors
Authors: Edwards Sarah , Mayat Nabilah 
Published: November 2024

AbstractBackgroundThe use of social media for learning amongst emergency medicine doctors has been increasing in recent years. However, the role of social media as a learning modality in emergency medicine is not fully understood. This study aims to understand why and how emergency medicine doctors use social media for learning. Through this understanding this study aims to promote thought into design of future resources of learning on social media.MethodsEmergency Medicine doctors of all grades were recruited, from a single tertiary University Hospital in the United Kingdom. These participants were interviewed by semi structured interview following the principles of a Critical Incident Technique. Recordings were professionally transcribed. Transcriptions were then thematically analysed and coded to understand participant’s perspectives. Ethics was granted by Cardiff University, Wales.Results20 emergency medicine doctors from Foundation Year 1 through to consultants were interviewed. Twitter (X) was the most popular platform; infographics were the most popular resource and 80% spent less than 3 hours per week on SM for learning. Key themes from the thematic analysis as to why emergency medicine doctors used social media for their learning included wanting to keep up to date ease of access, discussion around topics, bench marking current practice, community, and recommendations. Only 10% used social media as part of their continued professional development and 65% stated social media had influenced their clinical practice.ConclusionsThis unique qualitative explorative piece of work explores the use of social media for learning by emergency medicine doctors and how it is changing clinical practice.With the rapid growth and uptake in social media use for educational purposes. It is vital that all educators fully understand how it is being currently used as well as views of learners on this form of learning. This will allow us to further grow and develop this exciting area and maximise the educational impact on its users.What is already known about the subject?The use of social media for learning is popular amongst emergency medicine doctorsThe term FOAMed was first created following an Emergency Medicine Conference in 2012.There are increasing amounts of FOAMed resources produced each year related to emergency medicine.What this study adds?-X (Twitter) is a popular social media platform used by doctors-Information learnt from social media is being applied to clinical practice-Social media is being used for many reasons including to keep up to date, discussion around topics and bench marking of current practice with others-Learning through social media is being increasingly recognised as a form of Continued Professional Development (CPD) yet commonly not reported by learners as such.
Enhancing Recovery and Reducing Inflammation: The Impact of Enhanced Recovery After Surgery Recommendations on Inflammatory Markers in Laparoscopic Surgery – a Scoping review
Authors: Bersot Carlos Darcy Alves , Gomes Pereira Lucas Ferreira , Vieira Goncho Victor Gabriel , Guimaraes Pereira José Eduardo , Falcão Luiz Fernando dos Reis 
Published: November 2024

ABSTRACTIntroductionThe relationship between the Enhanced Recovery After Surgery (ERAS) guidelines and inflammatory markers in laparoscopic surgery has garnered increasing attention. These recommendations are designed to minimize surgical stress and potentially improve recovery outcomes by modifying perioperative care.ObjectiveThis scoping review aims to evaluate the impact of ERAS recommendations on inflammatory markers in patients undergoing laparoscopic surgeries, identifying current research gaps and consolidating findings from existing studies.MethodsGuided by the Cochrane Handbook for Systematic Reviews and adhering to the PRISMA-ScR guidelines, this review analyzed studies from databases like PubMed, Scopus, and Cochrane Library. We included both randomized controlled trials and observational studies that assessed inflammatory markers such as C-reactive protein (CRP), white blood cells (WBC), and Interleukin-6 (IL-6) in laparoscopic surgery patients managed with ERAS recommendations.ResultsOut of 64 initial studies, 7 met the inclusion criteria, involving a total of 2,047 patients. Most of the studies focused on laparoscopic colorectal surgeries. Commonly assessed markers were CRP and WBC. The findings consistently showed that ERAS guideline could mitigate the inflammatory response, evidenced by reduced levels of CRP and IL-6, which correlated with fewer postoperative complications and expedited recovery.ConclusionERAS recommendations appear to beneficially modulate inflammatory responses in laparoscopic surgery, which suggests a potential for enhanced recovery outcomes. However, the evidence is currently limited by the small number of studies and inherent methodological biases. Further robust RCTs are required to strengthen the evidence base and refine these protocols for broader clinical application.
Representational learning by optimization of neural manifolds in an olfactory memory network
Authors: Hu Bo , Temiz Nesibe Z. , Chou Chi-Ning , Rupprecht Peter , Meissner-Bernard Claire , Titze Benjamin , Chung SueYeon , Friedrich Rainer W. 
Published: November 2024

ABSTRACTHigher brain functions depend on experience-dependent representations of relevant information that may be organized by attractor dynamics or by geometrical modifications of continuous “neural manifolds”. To explore these scenarios we analyzed odor-evoked activity in telencephalic area pDp of juvenile and adult zebrafish, the homolog of piriform cortex. No obvious signatures of attractor dynamics were detected. Rather, olfactory discrimination training selectively enhanced the separation of neural manifolds representing task-relevant odors from other representations, consistent with predictions of autoassociative network models endowed with precise synaptic balance. Analytical approaches using the framework ofmanifold capacityrevealed multiple geometrical modifications of representational manifolds that supported the classification of task-relevant sensory information. Manifold capacity predicted odor discrimination across individuals, indicating a close link between manifold geometry and behavior. Hence, pDp and possibly related recurrent networks store information in the geometry of representational manifolds, resulting in joint sensory and semantic maps that may support distributed learning processes.
Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes
Authors: Patinios Constantinos , Gupta Darshana , Bassett Harris V. , Collins Scott P. , Kamm Charlotte , Kibe Anuja , Wang Yanyan , Zhao Chengsong , Vollen Katie , Toussaint Christophe , Polkoff Kathryn M. , Nguyen Thuan , Calvin Irene , Migur Angela , Al’Abri Ibrahim S. , Achmedov Tatjana , Del Re Alessandro , Saliba Antoine-Emmanuel , Crook Nathan , Stepanova Anna N. , Alonso Jose M. , Beisel Chase L. 
Published: November 2024

ABSTRACTBase editors create precise genomic edits by directing nucleobase deamination or removal without inducing double-stranded DNA breaks. However, a vast chemical space of other DNA modifications remains to be explored for genome editing. Here, we harness the bacterial anti-phage toxin DarT2 to append ADP-ribosyl moieties to DNA, unlocking distinct editing outcomes in bacteria versus eukaryotes. Fusing an attenuated DarT2 to a Cas9 nickase, we program site-specific ADP-ribosylation of thymines within a target DNA sequence. In tested bacteria, targeting drives efficient homologous recombination in tested bacteria, offering flexible and scar-free genome editing without base replacement nor counterselection. In tested eukaryotes including yeast, plants and human cells, targeting drives substitution of the modified thymine to adenine or a mixture of adenine and cytosine with limited insertions or deletions, offering edits inaccessible to current base editors. Altogether, our approach, called append editing, leverages the addition of a chemical moiety to DNA to expand current modalities for precision gene editing.
Mitochondria Regulate the Cell Fate Decisions of Megakaryocyte-Erythroid Progenitors
Authors: Sung Eunkyu , Murakami Shohei , Morita Masanobu , Ida Tomoaki , Akaike Takaaki , Motohashi Hozumi 
Published: November 2024

SummaryRecent studies highlight the critical role of mitochondria in hematopoiesis, especially in stem cell function and erythroid maturation. To explore mitochondrial contributions to cell lineage commitment of hematopoietic progenitors, we utilizedCars2mutant mice, an ideal model for this purpose. CARS2, a mitochondrial isoform of cysteinyl-tRNA synthetase, has cysteine persulfide synthase (CPERS) activity. Our new mouse model, with reduced CPERS activity, showed that theCars2mutation led to mitochondrial inhibition and anemia by suppressing erythroid commitment in megakaryocyte-erythroid progenitors (MEPs). This suppression was reproduced using mitochondrial electron transport chain inhibitors. We identified two distinct MEP populations based on the mitochondrial content: mitochondria-rich MEPs favored erythroid differentiation, while the mitochondria-poor MEPs favored megakaryocyte differentiation. These findings reveal critical contributions of mitochondria to the MEP lineage selection, acting as a “mitochondrial navigation” for lineage commitment.
Dispersion-induced
Q
-factor enhancement in waveguide-coupled surface lattice resonances
Authors: Kelavuori Jussi , Panahpour Ali , Huttunen Mikko J. 
Published: November 2024

Diffractively coupled nanoparticle arrays are promising candidates for helping to flatten many photonic devices such as lasers, lenses, and metrology instruments. Their performance, however, is directly linked with the size of the metasurfaces, limiting their applicability in nanophotonic applications. Here, we dramatically reduce array sizes of high-Q factor metasurfaces by utilizing strongly dispersive media. The effect is demonstrated by theoretically and numerically studying periodic arrays of plasmonic nanoparticles embedded inside Bragg-reflector waveguides. We demonstrate array dimensions reduction up to two orders of magnitude while still achieving ultrahigh-Q factors in excess of 104.

Published by the American Physical Society
2024