bluuebunny/crossref_metadata_2025 huggingface dataset:
RELATIONSHIP BETWEEN PARTICIPATION IN DAILY LIFE ACTIVITIES AND PHYSICAL ACTIVITY IN STROKE SURVIVORS: A PROTOCOL FOR A SYSTEMATIC REVIEW AND META-ANALYSES-BASED DATA SYNTHESIS
Authors: de Diego-Alonso Cristina , Blasco-Abadía Julia , Estellez Almudena Buesa , Giner-Nicolás Rafael , López-Royo María Pilar , Roldán-Pérez Patricia , Doménech-García Víctor , Bellosta-López Pablo , Fini Natalie A
Published: May 2023

Background

Stroke survivors undertake low levels of physical activity and participation in daily life activities, but there are no reviews on the relationship between physical activity and participation. This systematic review and meta-analyses-based data synthesis will aim to cross-sectionally and longitudinally describe and estimate the relationship between participation in daily life activities and physical activity in stroke survivors.

Methods and analysis

This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Six databases (PudMed, Web of Science, Scopus, PEDro, SPORTDiscus, and Rehabilitation & Sport Medicine Source) will be searched using terms grouped into three categories: stroke, physical activity, and participation in daily life activities. Observational and experimental studies assessing participation and physical activity levels in adult stroke survivors in English or Spanish will be included. The methodological quality of the studies will be assessed independently by 2 investigators, with the Newcastle-Ottawa scale. Study and sample characteristics, and physical activity and participation outcome data will be extracted. Additionally, if available, repeated measures and correlation values between physical activity and participation outcomes will be extracted. The Hedges-Olkin method will be used for pooling correlation values and a random-effects meta-analysis following restricted maximum likelihood estimation for pooling effect sizes of those studies prospectively assessing the same measures of participation and physical activity. Subgroup analyses will be performed if a sufficient number of studies are found. Heterogeneity between studies results will be analyzed using I2statistics, and publication bias will be examined using funnel plots and Egger’s tests.

Discussion

This will be the first systematic review with meta-analysis-based data synthesis to provide information on the relationship between physical activity and participation in stroke survivors. Findings are likely to inform, the design of health prevention protocols and the development of healthy behavior change interventions.
Bilateral retinofugal pathfinding impairments limit behavioral compensation in near-congenital one-eyedXenopus laevis
Authors: Forsthofer Michael , Gordy Clayton , Kolluri Meghna , Straka Hans
Published: May 2023

To generate a coherent visual percept, information from both eyes must be appropriately transmitted into the brain, where binocular integration forms the substrate for visuomotor behaviors. To establish the anatomical substrate for binocular integration, the presence of bilateral eyes and interaction of both optic nerves during retinotectal development play a key role. However, the extent to which embryonic monocularly derived visual circuits can convey visuomotor behaviors is unknown. In this study, we assessed the retinotectal anatomy and visuomotor performance of embryonically generated one-eyed tadpoles. In one-eyed animals, the axons of retinal ganglion cells from the singular remaining eye exhibited striking irregularities in their central projections in the brain, generating a non-canonical ipsilateral retinotectal projection. This data is indicative of impaired pathfinding abilities. We further show that these novel projections are correlated with an impairment of behavioral compensation for the loss of one eye.
A digital twin of bacterial metabolism during cheese production
Authors: Lecomte Maxime , Cao Wenfan , Aubert Julie , Sherman David James , Falentin Hélène , Frioux Clémence , Labarthe Simon
Published: May 2023

Cheese organoleptic properties result from complex metabolic processes occurring in microbial communities. A deeper understanding of such mechanisms makes it possible to improve both industrial production processes and end-product quality through the design of microbial consortia. In this work, we caracterise the metabolism of a three-species community consisting ofLactococcus lactis,Lactobacillus plantarumandPropionibacterium freudenreichiiduring a seven-week cheese production process. Using genome-scale metabolic models and omics data integration, we modeled and calibrated individual dynamics using monoculture experiments, and coupled these models to capture the metabolism of the community. This digital twin accurately predicted the dynamics of the community, enlightening the contribution of each microbial species to organoleptic compound production. Further metabolic exploration raised additional possible interactions between the bacterial species. This work provides a methodological framework for the prediction of community-wide metabolism and highlights the added-value of dynamic metabolic modeling for the comprehension of fermented food processes.
An Excitatory Projection from the Basal Forebrain to the Ventral Tegmental Area Underlying Anorexia-like Phenotypes
Authors: Cai Jing , Xu Yuanzhong , Jiang Zhiying , Jiang Yanyan , Young Claire , Li Hongli , Otiz-Guzman Joshua , Zhuo Yizhou , Li Yulong , Xu Yong , Arenkiel Benjamin R. , Tong Qingchun
Published: May 2023

Adaptation to potential threat cues in feeding regulation is key for animal survival. Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptation remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA). Glutamatergic neurons in both the BF and the VTA displayed correlated responses to various external stressors. Notably,in vivomanipulation of BF terminals in the VTA revealed that the glutamatergic BF➔VTA circuit reduces appetite, increases locomotion, and elicits avoidance. In consistence, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of anxiety, all hallmarks of typical anorexia phenotypes. Importantly, activation of BF glutamatergic terminals in the VTA reduced dopamine release in the nucleus accumbens (NAc). Collectively, our results point to overactivation of the glutamatergic BF➔VTA circuit as a potential cause of anorexia-like phenotypes involving reduced dopamine release.
Gastrointestinal transit mathematical model in mice treated with antibiotics
Authors: Maskawa Rie , Takayasu Lena , Takayasu Hideki , Watanabe Keiji , Takemine Shusuke , Kakimoto Takashi , Takeshita Kozue , Narushima Seiko , Suda Wataru , Takayasu Misako
Published: May 2023

Fecal pharmacokinetics is crucial in developing treatment design and evaluating gastrointestinal motility; however, it has not been yet elucidated. This study aimed to elucidate the fecal pharmacokinetics in mice orally administered vancomycin and establish a pharmacokinetic model with interpretable system parameters. In this study, we quantified the antibiotic concentrations in fecal samples collected at high frequency from C57BL/6J mice treated with single oral doses of low and high (1 and 20 mg/mL) concentrations of vancomycin. Samples were taken at approximately 4-hour intervals after administration of antibiotics, making it possible to track the dynamics of vancomycin in the feces with high resolution. Mice structurally pool contents in the stomach and cecum, so we constructed an intestinal transit model that compartmentalizes these organs. Two models were built based on the functional form of gastric content elimination, and physiological parameters such as gastric emptying and intestinal transit time were estimated using high-resolution actual data from each mouse. Fortunately, both models were suitable for evaluating the antibiotic concentrations in feces. By simulation, we confirmed that our estimates of model parameters, which are quite difficult to measure experimentally, are satisfactory. Importantly, this study is applicable to fundamental research relating to pharmacokinetics in the gastrointestinal tract.

NEW & NOTEWORTHY

This study tracked the pharmacokinetics of orally administered vancomycin by measuring its concentration in feces and described it using a mathematical model based on the physiological characteristics of mice to replicate these dynamics. As a predictive model, it allows for estimation of drug dynamics outside of the sampling time and extrapolation to individuals with different physiological characteristics.
A Comparative Study of Protein Structure Prediction Tools for Challenging Targets: Snake Venom Toxins
Authors: Kalogeropoulos Konstantinos , Bohn Markus-Frederik , Jenkins David E. , Ledergerber Jann , Sørensen Christoffer V. , Hofmann Nils , Wade Jack , Fryer Thomas , Nguyen Giang Thi Tuyet , auf dem Keller Ullrich , Laustsen Andreas H. , Jenkins Timothy P.
Published: May 2023

Protein structure determination is a critical aspect of biological research, enabling us to understand protein function and potential applications. Recent advances in deep learning and artificial intelligence have led to the development of several protein structure prediction tools, such as AlphaFold2 and ColabFold. However, their performance has primarily been evaluated on well-characterised proteins, and comparisons using proteins with poor reference templates are lacking. In this study, we evaluated three modelling tools on their prediction of over 1000 snake venom toxin structures with no reference templates. Our findings show that AlphaFold2 (AF2) performed the best across all assessed parameters. We also observed that ColabFold (CF) only scored slightly worse than AF2, while being computationally less intensive. All tools struggled with regions of intrinsic disorder, such as loops and propeptide regions, and performed well in predicting the structure of functional domains. Overall, our study highlights the importance of exercising caution when working with proteins that have poor reference templates, are large, and contain flexible regions. Nonetheless, leveraging computational structure prediction tools can provide valuable insights into the modelling of protein interactions with different targets and reveal potential binding sites, active sites, and conformational changes, as well as into the design of potential molecular binders for reagent, diagnostic, or therapeutic purposes.

Statement

Recent advances in machine learning have led to the development of new protein structure prediction tools. However, these tools have mainly been tested on well-known proteins and their performance on proteins without known templates is unclear. This study evaluated the performance of three tools on over 1000 snake venom toxins. We found that while caution is required when studying poorly characterised proteins, these tools offer valuable opportunities to understand protein function and applications.
Introgression of a dominant phototropin1 mutant superenhances carotenoids and boosts flavor-related volatiles in genome-edited tomatoRINmutants
Authors: Nizampatnam Narasimha Rao , Sharma Kapil , Gupta Prateek , Pamei Injangbuanang , Sarma Supriya , Sreelakshmi Yellamaraju , Sharma Rameshwar
Published: May 2023

The tomato (Solanum lycopersicum) ripening inhibitor (rin) mutation is known to completely repress fruit ripening. The heterozygous (RIN/rin) fruits have extended shelf life, ripen normally, but have poor taste and flavour. Even the CRISPR/Cas9-generatedrinalleles have these undesirable attributes associated with therinmutation. To address this, we used genome editing to generate newer alleles ofRIN(rinCR) by targeting the K domain, which is essential for the oligomerization of MADS-box transcription factors. Unlike previously reported CRISPR alleles, therinCRalleles displayed delayed onset of ripening, suggesting that the mutated K domain represses the onset of ripening. TherinCRfruits had extended shelf life and accumulated carotenoids at an intermediate level betweenrinand wild-type parent. Besides, the metabolites and hormonal levels inrinCRfruits were more akin torin. To overcome the negative attributes ofrin, we crossed therinCRalleles withNps1, which enhances carotenoid levels in tomato fruits.Nps1harbours a dominant-negative mutation in the plant photoreceptor phototropin1. The resultingNps1/rinCRhybrids had extended shelf life and 4.4-7.1-fold higher carotenoid levels than the wild-type parent. TheNps1/rinCRfruits had higher auxin and reduced ABA levels, which are reportedly linked with slower ripening. The metabolome ofNps1/rinCRfruits revealed higher sucrose, malate, and volatiles associated with tomato taste and flavour. Notably, the boosted volatile levels inNps1/rinCRwere only observed in fruits bearing the homozygousNps1(Nps1/Nps1) mutation. Our findings suggest that theNps1introgression into tomato ripening mutants provides a promising strategy for developing tomato cultivars with extended shelf life, improved taste, and flavour.
Mesoscale simulation of biomembranes with FreeDTS
Authors: Pezeshkian Weria , Ipsen John H.
Published: May 2023

We present FreeDTS software for performing computational research on biomembranes at the mesoscale. In this software, a membrane is represented by a dynamically triangulated surface equipped with vertex-based inclusions to integrate the effects of integral and peripheral membrane proteins. Several algorithms are included in the software to simulate complex membranes at different conditions such as framed membranes with constant tension, vesicles and high-genus membranes with various fixed volumes or constant pressure differences and applying external forces to membrane regions. Furthermore, the software allows the user to turn off the shape evolution of the membrane and focus solely on the organization of proteins. As a result, we can take realistic membrane shapes obtained from, for example, cryo-electron tomography and backmap them into a finer simulation model. In addition to many biomembrane applications, this software brings us a step closer to simulating realistic biomembranes with molecular resolution. Here we provide several interesting showcases of the power of the software but leave a wide range of potential applications for interested users.
Deciphering the rule of antigen-antibody amino acid interaction
Authors: Jiang Min , Fang Changyin , Ma Yongping
Published: May 2023

Antigenic drift is the biggest challenge for mutagenic RNA virus vaccine development. The most fundamental but neglected thing is to determine the immune escape mutation map (IEMM) of 20 amino acids to reveal the rule of the viral immune escape. We use universal protein tags as a linear epitope model to determine the relationship between the epitope mutation and immune escape. To describe and draw amino acid interaction maps, mutations of protein tags are classified into four types: IEM (immune escape mutation), ADERM (antibody-dependent enhancement risk mutation), EQM (equivalent mutation), and IVM (invalid mutation). To make up for the data limitation, the amino acid interaction pairs determined by 3D structure through literature search are simultaneously used to form a more systematic and universal antigen-antibody interaction maps. The results are: (i) one residue interacts with multiple amino acids in antigen-antibody interaction; (ii) Most amino acid replacements are IVM and EQM. (iii) Once aromatic amino acids replace non-aromatic amino acids, the mutation is often inactive. (iv) Substituting residues with the same physical and chemical properties easily lead to IEM. Therefore, this study had important theoretical significance for future research on antigenic drift, antibody rescue and vaccine renewal design.

Importance

We typed the antigenic epitope mutations into IEM, ADERM, EQM, and IVM types to describe and quantify the results of antigenic mutations. According to the results, the antigen-antibody interaction rule was summarized as one-to-many interaction rule. To sum up, the Epitope mutation rules were defined as IVM and EQM predomination rule, aryl mutation escape rule and homogeneous mutation escape rule.
Skin permeable polymer for noninvasive transdermal insulin delivery
Authors: Wei Qiuyu , He Zhi , Xiang Jiajia , Piao Ying , Huang Jianxiang , Geng Yu , Zhu Haoru , Li Zifan , Zeng Jiaheng , Zhang Yan , Lu Hongrui , Zhou Quan , Shao Shiqun , Tang Jianbin , Zhou Zhuxian , Zhou Ruhong , Shen Youqing
Published: May 2023

Subcutaneous injection of insulin is the current standard medication for many diabetic patients. Convenient and painless noninvasive transdermal insulin delivery has long been pursued but yet succeeded due to no such technologies for large biomacromolecules. We find a tertiary amine oxide-based polyzwitterion, OPDMA, that can efficiently penetrate both the stratum corneum (SC) and viable epidermis into circulation. So its conjugate with insulin, OPDMA-I, applied on the skin can exhibit hypoglycemic effects as efficiently as subcutaneously injected insulin in type-1 diabetic mice and minipigs. The unique pH-dependent cationic-to-zwitterionic transition of OPDMA in the characteristic acidic-to-neutral pH gradient from the skin surface to deep SC enables fast transdermal delivery of OPDMA and its conjugate. On the skin, OPDMA binds to carboxylic acids in the acidic sebum layer, enriching OPDMA-I on the SC. As pH increases in deeper SC layers, binding between OPDMA-I and the skin weakens gradually, allowing for diffusion through inter-corneocyte gaps and penetration into viable epidermis and finally entering the systemic circulation via dermal lymphatic vessels. This process does not alter SC microstructures or cause any physiological changes in the skin. This study represents a groundbreaking example of noninvasive transdermal protein delivery.
Pangenome calculation beyond the species level using RIBAP: A comprehensive bacterial core genome annotation pipeline based on Roary and pairwise ILPs
Authors: Lamkiewicz Kevin , Barf Lisa-Marie , Sachse Konrad , Hölzer Martin
Published: May 2023

Pangenome analysis is a computational method for identifying genes that are present or absent from a group of genomes, which helps to understand evolutionary relationships and to identify essential genes. While current state-of-the-art approaches for calculating pangenomes comprise various software tools and algorithms, these methods can have limitations such as low sensitivity, specificity, and poor performance on specific genome compositions. A common task is the identification of core genes, i.e., genes that are present in (almost) all input genomes. However, especially for species with high sequence diversity, e.g., higher taxonomic orders like genera or families, identifying core genes is challenging for current methods. We developed RIBAP (Roary ILP Bacterial core Annotation Pipeline) to specifically address these limitations. RIBAP utilizes an integer linear programming (ILP) approach that refines the gene clusters initially predicted by the pangenome pipeline Roary. Our approach performs pairwise all-versus-all sequence similarity searches on all annotated genes for the input genomes and translates the results into an ILP formulation. With the help of these ILPs, RIBAP has successfully handled the complexity and diversity ofChlamydia, Klebsiella, Brucella, and Enterococcusgenomes, even when genomes of different species are part of the analysis. We compared the results of RIBAP with other established and recent pangenome tools (Roary, Panaroo, PPanGGOLiN) and showed that RIBAP identifies all-encompassing core gene sets, especially at the genus level. RIBAP is freely available as a Nextflow pipeline under the GPL3 license:https://github.com/hoelzer-lab/ribap.
Neural representation strength of predicted category features biases decision behavior
Authors: Yan Yuening , Zhan Jiayu , Garrod Oliver , Cui Xuan , Ince Robin A.A. , Schyns Philippe G.
Published: May 2023

Theories of prediction-for-perception propose that the brain predicts the information contents of upcoming stimuli to facilitate their perceptual categorization. A mechanistic understanding should therefore address where, when, and how the brain predicts the stimulus features that change behavior. However, typical approaches do not address these predicted stimulus features. Instead, multivariate classifiers are trained to contrast the bottom-up patterns of neural activity between two stimulus categories. These classifiers then quantify top-down predictions as reactivations of the category contrast. However, a category-contrast cannot quantify the features reactivated for each category–which might be from either category, or both. To study the predicted category-features, we randomly sampled features of stimuli that afford two categorical perceptions and trained multivariate classifiers to discriminate the features specific to each. In a cueing design, we show where, when and how trial-by-trial category-feature reactivation strength directly biases decision behavior, transforming our conceptual and mechanistic understanding of prediction-for-perception.
Insights from a genome-wide truth set of tandem repeat variation
Authors: Weisburd Ben , Tiao Grace , Rehm Heidi L.
Published: May 2023

Tools for genotyping tandem repeats (TRs) from short read sequencing data have improved significantly over the past decade. Extensive comparisons of these tools to gold standard diagnostic methods like RP-PCR have confirmed their accuracy for tens to hundreds of well-studied loci. However, a scarcity of high-quality orthogonal truth data limited our ability to measure tool accuracy for the millions of other loci throughout the genome. To address this, we developed a TR truth set based on the Synthetic Diploid Benchmark (SynDip). By identifying the subset of insertions and deletions that represent TR expansions or contractions with motifs between 2 and 50 base pairs, we obtained accurate genotypes for 139,795 pure and 6,845 interrupted repeats in a single diploid sample. Our approach did not require running existing genotyping tools on short read or long read sequencing data and provided an alternative, more accurate view of tandem repeat variation. We applied this truth set to compare the strengths and weaknesses of widely-used tools for genotyping TRs, evaluated the completeness of existing genome-wide TR catalogs, and explored the properties of tandem repeat variation throughout the genome. We found that, without filtering, ExpansionHunter had higher accuracy than GangSTR and HipSTR over a wide range of motifs and allele sizes. Also, when errors in allele size occurred, ExpansionHunter tended to overestimate expansion sizes, while GangSTR tended to underestimate them. Additionally, we saw that widely-used TR catalogs miss between 16% and 41% of variant loci in the truth set. These results suggest that genome-wide analyses would benefit from genotyping a larger set of loci as well as further tool development that builds on the strengths of current algorithms. To that end, we developed a new catalog of 2.8 million loci that captures 95% of variant loci in the truth set, and created a modified version of ExpansionHunter that runs 2 to 3x faster than the original while producing the same output.
Theranostic gold in a gold cage nanoparticle for photothermal ablation and photoacoustic imaging of skin and oral infections
Authors: Hajfathalian Maryam , de Vries Christiaan R. , Hsu Jessica C. , Amirshaghaghi Ahmad , Dong Yuxi C. , Ren Zhi , Liu Yuan , Huang Yue , Li Yong , Knight Simon , Jonnalagadda Pallavi , Zlitni Aimen , Grice Elizabeth , Bollyky Paul L. , Koo Hyun , Cormode David. P.
Published: May 2023

Abstract

Biofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we describe a unique structure of dextran coated gold in a gold cage nanoparticle that enables photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser can selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observe a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections respectively. These effects were over 100 times greater than that seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We conclude that photothermal ablation using theranostic nanoparticles is a rapid, precise, and non-toxic method to detect and treat biofilm-associated infections.
TGF-β Ligand Cross-Subfamily Interactions in the Response ofCaenorhabditis elegansto Bacterial Pathogens
Authors: Ciccarelli Emma Jo , Wing Zachary , Bendelstein Moshe , Johal Ramandeep Kaur , Singh Gurjot , Monas Ayelet , Savage-Dunn Cathy
Published: May 2023

The Transforming Growth Factor beta (TGF-β) family consists of numerous secreted peptide growth factors that play significant roles in cell function, tissue patterning, and organismal homeostasis, including wound repair and immunity. Typically studied as homodimers, these ligands have the potential to diversify their functions through ligand interactions that are synergistic, cooperative, additive, and/or antagonistic. In the nematodeCaenorhabditis elegans, there are only five TGF-β ligands, providing an opportunity to dissect ligand interactions in fewer combinations than in vertebrates. As in vertebrates, these ligands can be divided into bone morphogenetic protein (BMP) and TGF-β/Activin subfamilies that predominantly signal through discrete signaling pathways. The BMP subfamily ligand DBL-1 has been well studied for its role in the innate immune response inC. elegans. Here we show that all five TGF-β ligands play a role in the immune response. We also demonstrate that multiple TGF-β ligands act cooperatively as part of this response. We show that the two BMP-like ligands – DBL-1 and TIG-2 – function independently of each other in the immune response, while TIG-2/BMP and the TGF-β/Activin-like ligand TIG-3 function cooperatively. Structural modeling supports the potential for TIG-2 and TIG-3 to form heterodimers. Finally, we show that canonical DBL-1/BMP receptor and Smad signal transducers function in the response to bacterial pathogens, while components of the DAF-7 TGF-β/Activin signaling pathway do not play a role in survival. These results demonstrate a novel potential for BMP and TGF-β/Activin subfamily ligands to interact, and may provide a mechanism for distinguishing the developmental and homeostatic functions of these ligands from an acute response such as the innate immune response to bacterial pathogens.
Association of Seizure with COVID-19 Vaccines in Persons with Epilepsy: A Systematic Review and Meta-analysis
Authors: Rafati Ali , Jameie Melika , Amanollahi Mobina , Jameie Mana , Pasebani Yeganeh , Sakhaei Delaram , Ilkhani Saba , Rashedi Sina , Pasebani Mohammad Yazdan , Azadi Mohammadreza , Rahimlou Mehran , Kwon Churl-Su
Published: May 2023

Objective

Seizure following immunization, especially in persons with epilepsy (PwE), has long been a concern, and seizure aggravation followed by Coronavirus Disease 2019 (COVID-19) vaccines is a serious issue for PwE. The immunization rate in PwE has been lower compared to same-age controls due to vaccine hesitancy and concerns about seizure control. Herein, we systematically reviewed the seizure activity-related events in PwE following COVID-19 vaccination.

Methods

Four search engines were searched from inception until January 31, 2023, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. Random- and fixed-effect models using the logit transformation method were used for meta-analysis. The quality of the studies was evaluated by the Newcastle-Ottawa scale. Outcomes of interest included (a) pooled proportion of increased seizure frequency and (b) pooled incidence proportion of status epilepticus (SE) in PwE receiving COVID-19 vaccines.

Results

Of the 2207 studies identified, 18 met eligibility criteria, of which 16 entered the meta-analysis. The pooled proportion of increased seizure frequency (16 studies-4197 PwE) was 5% (95CI: 3%-6%, I2=57%), further subcategorized into viral vector (3%, 95CI: 2%-7%, I2=0%), mRNA (5%, 95CI: 4%-7%, I2=48%), and inactivated (4%, 95CI: 2%-8%, I2=77%) vaccines. The pooled incidence proportion of SE (15 studies-2480 PwE) was 0.08% (95CI: 0.02%-0.32%, I2=0%), further subcategorized into the viral vector (0.00%, 95CI: 0.00%-1.00%, I2=0%), mRNA (0.09%, 95CI: 0.01%-0.62%, I2=0%), and inactivated (0.00%, 95CI: 0.00%-1.00%, I2=0%) vaccines. No significant difference was observed between mRNA and viral vector vaccines (5 studies, 1122 vs. 198 PwE, respectively) regarding increased seizure frequency (OR: 1.10, 95CI: 0.49-2.50, p-value=0.81, I2=0%).

Significance

The meta-analysis proposed a 5% increased seizure frequency following COVID-19 vaccination in PwE, with no difference between mRNA and viral vector vaccines. Furthermore, we found a 0.08% incidence proportion for SE. While this safety evidence is noteworthy, this cost should be weighed against vaccination benefits.
ChatGPT in medical literature – a concise review and SWOT analysis
Authors: Gödde Daniel , Nöhl Sophia , Wolf Carina , Rupert Yannik , Rimkus Lukas , Ehlers Jan , Breuckmann Frank , Sellmann Timur
Published: May 2023

Background

ChatGPT (Chat Generative Pre-trained Transformer) has initiated widespread conversation across various human sciences. We here performed a concise review combined with a SWOT (strengths, weaknesses, opportunities, threats) analysis on ChatGPT potentials in natural science including medicine.

Methods

This is a concise review of literature published in PUBMED from 01.12.2022 to 31.03.2023. The only search term used was “ChatGPT”. Publications metrics (author, journal, and subdisciplines thereof) as well as findings of the SWOT analysis are presented.

Findings

Of 178 studies in total, 160 could be evaluated. The average impact factor was 4,423 (0 – 96,216), average publication speed was 16 days (0-83 days). Of all articles, there were 77 editorials, 43 essays, 21 studies, six reviews, six case reports, six news, and one meta-analyses. Strengths of ChatGPT include well-formulated expression as well as the ability to formulate general contexts flawlessly and comprehensibly, whereas the time-limited scope as well as the need for correction by experts were identified as weaknesses and threats. Opportunities include assistance in formulating medical issues for non-native speakers as well as the chance to be involved in the development of such AI in a timely manner.

Interpretation

Artificial intelligences such as ChatGPT will revolutionize more than just the medical publishing landscape. One of the biggest dangers in this is uncontrolled use, so we would do well to establish control and security measures at an early stage.

Research in context

Evidence before this study

Since its release in 11/ 2022, only a few randomized controlled trials using ChatGPT have been published. To date, the majority of data stems from short notes or communication. Given the enormous interest (and also potential for misuse), we conducted a PUBMED literature search to create the most comprehensive evidence base currently available. We searched PUBMED for publications including the quote “ChatGPT” in English or German from 01.12.2022 until 31.03.2023. In order not risk any bias of evidence all related publications were screened initially.

Added value of this study

This is the most concise review for ChatGPT up to date. By means of a SWOT analysis, readers and researchers gain comprehensive insight to strengths, weaknesses, opportunities and threats of ChatGPT especially in the context of medical literature.

Implications of all the available evidence

Our review may well serve as origin for further research related to the topic in order to create more evidence, strict regulations and policies in dealing with ChatGPT.
SanPy: A whole-cell electrophysiology analysis pipeline
Authors: Guarina Laura , Le Johnson Tran , Griffith Theanne N , Santana Luis Fernando , Cudmore Robert H
Published: May 2023

The analysis of action potentials and other membrane voltage fluctuations provide a powerful approach for interrogating the function of excitable cells. Yet, a major bottleneck in the interpretation of this critical data is the lack of intuitive, agreed upon software tools for its analysis. Here, we present SanPy, a Python-based open-source and freely available software pipeline for the analysis and exploration of whole-cell current-clamp recordings. SanPy provides a robust computational engine with an application programming interface. Using this, we have developed a cross-platform graphical user interface that does not require programming. SanPy is designed to extract common parameters from action potentials including threshold time and voltage, peak, half-width, and interval statistics. In addition, several cardiac parameters are measured including the early diastolic duration and rate. SanPy is built to be fully extensible by providing a plugin architecture for the addition of new file loaders, analysis, and visualizations. A key feature of SanPy is its focus on quality control and data exploration. In the desktop interface, all plots of the data and analysis are linked allowing simultaneous data visualization from different dimensions with the goal of obtaining ground truth analysis. We provide documentation for all aspects of SanPy including several use cases and examples. To test SanPy, we have performed analysis on current-clamp recordings from heart and brain cells. Taken together, SanPy is a powerful tool for whole-cell current-clamp analysis and lays the foundation for future extension by the scientific community.

News and Noteworthy

Whole-cell current-clamp recording is a critical technique to understand detailed biophysical mechanisms at the cellular and network levels. Yet, the analysis of this data is by no means standardized. Here, we present SanPy, a Python based open-source software pipeline for the exploration and analysis of current-clamp recordings. SanPy provides a powerful computational engine with an application programming interface. Finally, SanPy provides a cross-platform point-and-click graphical user interface that does not require programming.
Genome-scale analysis of interactions between genetic perturbations and natural variation
Authors: Hale Joseph J. , Matsui Takeshi , Goldstein Ilan , Mullis Martin N. , Roy Kevin R. , Ville Chris Ne , Miller Darach , Wang Charley , Reynolds Trevor , Steinmetz Lars M. , Levy Sasha F. , Ehrenreich Ian M.
Published: May 2023

Interactions between genetic perturbations and segregating loci can cause perturbations to show different phenotypic effects across genetically distinct individuals. To study these interactions on a genome scale in many individuals, we used combinatorial DNA barcode sequencing to measure the fitness effects of 7,700 CRISPRi perturbations targeting 1,712 distinct genes in 169 yeast cross progeny (or segregants). We identified 460 genes whose perturbation has different effects across segregants. Several factors caused perturbations to show variable effects, including baseline segregant fitness, the mean effect of a perturbation across segregants, and interacting loci. We mapped 234 interacting loci and found four hub loci that interact with many different perturbations. Perturbations that interact with a given hub exhibit similar epistatic relationships with the hub and show enrichment for cellular processes that may mediate these interactions. These results suggest that an individual’s response to perturbations is shaped by a network of perturbation-locus interactions that cannot be measured by approaches that examine perturbations or natural variation alone.
Endogenous fine-mapping of functional regulatory elements in complex genetic loci
Authors: Zhao Ke , Zhou Yao , Wu Chengyue , Wang Jianhua , Yao Hongcheng , Cheng Xin , Zhao Lin , Wang Wei , Chu Xinlei , Yi Xianfu , Chen Yupeng , Li Miaoxin , Lu Wange , Chen Kexin , Sham Pak Chung , Li Mulin Jun
Published: May 2023

The vast majority of genetic loci associated with polygenic complex traits are located in non-coding regions of the human genome. However, many of these regions exhibit high- order gene regulatory relationships and complicated linkage disequilibrium (LD) configurations, which bring challenges to accurately identify causal variants and their target genes controlling specific molecular processes or traits. We employed multiplexed single-cell CRISPR interference and activation perturbations to explore the links betweencis-regulatory element (CRE) and target gene expression within tight LD in the endogenous chromatin context. We validated the prevalence of multiple causality in perfect LD (pLD) for independent expression quantitative trait locus (eQTL), and revealed fine-grained genetic effects on gene expression within pLD. These effects are difficult to decipher using conventional eQTL fine-mapping or to predict via existing computational methods. We found that nearly half of the casual CREs lack classical epigenetic markers, potentially affecting gene expression through hidden regulatory mechanisms. Integrative analysis on different types of perturbation effects suggested a high regulatory plasticity of the human genome. These findings will propel further in-depth exploration of functional genomic elements, facilitating a more comprehensive understanding of gene expression regulatory patterns and the development of complex traits.
Apposed networks of interacting TCRs and BCRs exhibiting mosaicked CDR3 sequences made of fixed junctional motifs
Authors: Ahmed Rizwan , Majety Neha , Chan Kevin C. , Giwa Adebola , Heinemann Joseph , Zhang Hao , Margolick Joseph , Al-Hallaf Rafid , Paul Prajita , Bell David R. , Song Yi , Lee Sangyun , Zhou Ruhong , Wolfe Risa M , Donner Thomas , Jie Chunfa , Hamad Abdel Rahim A
Published: May 2023

T and B cells are the two arms of the adaptive immune system that mediate cellular and humoral immunity, respectively, using highly diverse repertoires of antigen receptors. T cells recognize antigens using the T cell receptor (TCR), whereas B cells use the B cell receptor (BCR or surface immunoglobulin). Complementary determining regions (CDR3) of TCRs and BCRs are randomly generated through somatic VDJ recombination and nucleotide deletions and insertions at the V-D and D-J junctions. Contrary to this paradigm, here we describe two networks of millions of TCRβ and IGH clonotypes that are made from only two CDR3 sequences and associated with more 63 diseases. The TCRβ network members bore either the prototypic signature CDR3 sequence (CASSPGTEAFF), its N-terminal VD motif (CASSPGT) recombined with various Jβ segments (CASSPGT-Jβx) or its DJβ motif recombined with various Vβ (Vβx-PGTEAFF). The BCR network members exhibit one signature CDR3 sequence (CARx1-4DTAMVYYFYDW) made from an invariant DJH motif (DTAMVYYFDYW) combined with various VH genes. The prototypes of the two networks are apparently teleogically related as they were dually expressed on the rare population of dual expresser (DE) lymphocytes and molecular dynamic simulations show that they were interacting partners. We conclude that members of the two networks represent a core set of evolutionary-conserved primordial antigen receptors that play fundamental roles in host defense and autoimmune diseases.
Swimming ability of theCarybdea marsupialis(Cnidaria: Cubozoa: Carybdeidae): implications for its spatial distribution
Authors: Bordehore Cesar , Manchado-Pérez Sara , Fonfría Eva S.
Published: May 2023

Although usually considered part of the plankton, cubozoans are strong swimmers. The aim of this study was to determine the influence of the active swimming ability of the box jellyfishCarybdea marsupialison the spatial distribution of a well-studied population off Dénia (NW Mediterranean) where adults and juveniles do not overlap geographically. To achieve this aim, we analyzed the swimming speed, proficiency, effective velocity, and effective displacement index (EDI) of 27 individuals with diagonal bell widths (DBW) ranging from 1.1 to 36 mm. The laboratory analysis utilized conventional video recordings and the video analysis tool Tracker. Mean swimming speed for small juveniles (DBW ≤ 5 mm), medium juveniles (5 mm < DBW< 15 mm) and adults (DBW ≥ 15 mm) were 9.65 ± 0.76 mm-1, 21.91 ± 2.29 mm-1and 43.10 ± 1.78 mm-1(mean ± s.e.m.), respectively. Comparing these results with the local currents obtained from drifting buoys analyzed in the area over the course of three years, adults would be able to swim strongly enough to overcome almost 70% of the currents, whereas the small juveniles would not reach 17%. This allows larger individuals to select their habitat, while smaller individuals are left dependent on advection. Although experiments adding currents in aquaria would be necessary to confirm these theoretical results, the data obtained would be useful in improving the performance of bio-mathematical models used to predict jellyfish blooms since, even though the sting ofC. marsupialisis non-fatal, it may produce systemic effects in sensitive swimmers.

Summary statement

The analysis of the swimming ability ofC. marsupialiselucidates its key role in the spatial distribution of a northwestern Mediterranean population.
Temporal Dynamics of Brain Activity Predicting Sense of Agency over Muscle Movements
Authors: Veillette John P. , Lopes Pedro , Nusbaum Howard C.
Published: May 2023

Our muscles are the primary means through which we affect the external world, and the sense of agency (SoA) over the action through those muscles is fundamental to our self-awareness. However, SoA research to date has focused almost exclusively on agency over action outcomes rather than over the musculature itself, as it was believed that SoA over the musculature could not be manipulated directly. Drawing on methods from human-computer interaction and adaptive experimentation, we use human-in-the-loop Bayesian optimization to tune the timing of electrical muscle stimulation so as to robustly elicit a sense of agency over electrically-actuated muscle movements in male and female human subjects. We use time-resolved decoding of subjects’ EEG to estimate the time course of neural activity which predicts reported agency on a trial-by-trial basis. Like paradigms which assess SoA over action consequences, we found that the late (post-conscious) neural activity predicts SoA. Unlike typical paradigms, however, we also find patterns of early (sensorimotor) activity with distinct temporal dynamics predicts agency over muscle movements, suggesting that the “neural correlates of agency” may depend on the level of abstraction (i.e., direct sensorimotor feedback vs. downstream consequences) most relevant to a given agency judgement. Moreover, fractal analysis of the EEG suggests that SoA-contingent dynamics of neural activity may modulate the sensitivity of the motor system to external input.

Significance Statement

The sense of agency – the feeling of “I did that” – when directing one’s own musculature is a core feature of human experience. We show that we can robustly manipulate the sense of agency over electrically actuated muscle movements, and we investigate the time course of neural activity that predicts the sense of agency over these actuated movements. We find evidence of two distinct neural processes – a transient sequence of patterns that begins in the early sensorineural response to muscle stimulation and a later, sustained signature of agency. These results shed light on the neural mechanisms by which we experience our movements as volitional.
Grid Cells, Border Cells and Discrete Complex Analysis
Authors: Dabaghian Yuri
Published: May 2023

We propose a mechanism enabling the appearance of border cells—neurons firing at the boundaries of the navigated enclosures. The approach is based on the recent discovery of discrete complex analysis on a triangular lattice, which allows constructing discrete epitomes of complex-analytic functions and making use of their inherent ability to attain maximal values at the boundaries of generic lattice domains. As it turns out, certain elements of the discrete-complex framework readily appear in the oscillatory models of grid cells. We demonstrate that these models can extend further, producing cells that increase their activity towards the frontiers of the navigated environments. We also construct a network model of neurons with border-bound firing that conforms with the oscillatory models.
Prevalence of short peer reviews in leading general medical journals: a study of peer-review length at The BMJ, PLOS Medicine, and BMC Medicine
Authors: Geldsetzer Pascal , Heemann Markus , Tikka Pauli , Wang Grace , Cusick Marika Mae , Lenjani Ali , Krishnan Nandita
Published: May 2023

Background

High-quality peer reviews are often thought to be essential to ensuring the integrity of the scientific publication process but measuring peer review quality is challenging. Although imperfect, review word count could serve as a simple, objective metric of review quality. We aimed to examine the prevalence of very short reviews and how often they inform editorial decisions on research articles in leading general medical journals.

Methods

We compiled a data set of peer reviews from published full-length original research articles in The BMJ, BMC Medicine, and PLOS Medicine for the years 2003 to 2022. In our primary analyses, we used a threshold of <200 words to calculate the prevalence of very short reviews. In secondary analyses, we also used thresholds of <100 and <300 words. In addition to disaggregating results by journal and year, we plotted the proportion of articles for which the first editorial decision was made based on a set of peer reviews in which very short reviews constituted 100%, ≥50%, ≥33%, or ≥20% of the reviews.

Results

In this sample of 11,466 reviews corresponding to 4,038 published articles, the median review word count was 425 (Interquartile Range=253–675), and the mean was 520 (Standard Deviation=401). The overall prevalence of very short (<200 words) reviews was 17.1% [95% CI: 16.4%–17.8%]. Across the three journals, 20.9% [95% CI: 19.6%–22.2%] of initial editorial decisions were based on review sets containing ≥50% very short reviews. The prevalence of very short reviews and share of editorial decisions based on review sets containing ≥50% very short reviews was highest for BMC Medicine at 26.8% [95% CI: 25.1%–28.5%] and lowest for The BMJ at 7.3% [95% CI: 5.7%–8.9%].

Conclusions

A substantial proportion of initial editorial decisions for published articles in these three leading general medical journals was based on peer reviews of such short length that they were unlikely to be of high quality. Future research should determine whether monitoring peer review length is a useful approach to improving the quality of the peer review process and which interventions, such as incentives and norm-based interventions, are most effective in soliciting more detailed reviews.