bluuebunny/crossref_metadata_2025 huggingface dataset:
The linear viscoelastic fracture theory applies to soft solids better when they are…viscoelastic
Authors: Barthel Etienne
Published: April 2024

Over the last half-century, linear viscoelastic models for crack growth in soft solids have flourished but their predictions have rarely been compared to experiments. In fact, most available models are either very approximate or cast in forms which are not quite suitable for the analysis of actual data. Here, we propose a linear viscoelastic approach which consistently exploits the dynamic mechanical analysis data. We apply this method to four sets of results documenting fracture or adhesion rupture in soft solids with various degrees of viscoelasticity. For elastomers, the results reproduce the well-known inconsistency of the process zone size. In more viscoelastic systems, however, the present approach is able to match the measured velocity dependence of the rupture energy with physically acceptable process zone sizes. Moreover, our predictions agree with the damage zone sizes measured by mechanoluminescence. Building on these results, we discuss various issues arising when evaluating the linear viscoelastic contribution to the rupture/adhesion energy in soft solids: data quality, physical interpretation of the parameters, validity of simpler approximations and limitations of the present approach.
Axisymmetric blockfold origami: a non-flat-foldable Miura variant with self-locking mechanisms and enhanced stiffness
Authors: Dang Xiangxin , Paulino Glaucio H.
Published: April 2024

Origami foldcores, especially the blockfold cores, have emerged as promising components of high-performance sandwich composites. Inspired by the blockfold origami, we propose the axisymmetric blockfold origami (ABO), which is composed of both rectangular and trapezoidal panels. The ABO inherits the non-flat-foldability of the blockfold origami, and furthermore, displays self-locking mechanisms and enhanced stiffness. The geometry and folding kinematics of the ABO are formulated with respect to the geometric parameters and the folding angle of the assembly. The mathematical conditions are derived for the existence of self-locking mechanisms. We perform compression test simulations to demonstrate enhanced stiffness and increased load-bearing capacity. We find that the existence of rectangular panels not only dominates the non-flat-foldability of the ABO, but also contributes to the enhancement of the stiffness. Our results suggest the potential applications of the ABO for building load-bearing structures with rotational symmetry. Moreover, we discuss the prospects of designing tightly assembled multi-layered origami structures with prestress induced by the mismatch of successive layers to enlighten future research.
Inducible clindamycin resistance among clinical Gram-positive cocci in a tertiary hospital in Niger Republic
Authors: Yacouba Abdourahamane , Alassoum Malika Zeidou , Soumana Boubacar Marou , Saley Sahada Moussa , Ousmane Abdoulaye , Moussa Harouna , Amatagas Saidou , Alhousseini Daouda , Doutchi Mahamadou , Chaibou Salaou , Daou Mamane , Brah Souleymane , Adehossi Eric , Olowo-Okere Ahmed , Mamadou Saidou
Published: April 2024

Background. Macrolide-induced resistance to clindamycin is a well-described mechanism leading to treatment failure. Herein, we determined the frequency and associated factors of inducible clindamycin resistance in Gram-positive cocci in a tertiary care hospital.
Methods. A cross-sectional descriptive study was carried out between January and December 2022. D tests were performed as recommended by EUCAST 2021 guidelines on 100 non-duplicate clinical isolates of Gram-positive cocci to determine the prevalence of methicillin resistance and inducible clindamycin resistance among the collected isolates.
Results. Of the 100 Gram-positive cocci isolates, 56 (56.0 %), 17 (17.0 %) and 27 (27.0 %) were respectively coagulase-negative staphylococci, Staphylococcus aureus and Streptococcus spp. Among Streptococcus spp., Group D Streptococci (15.0%) were the most isolated. Methicillin-resistant Staphylococcusaureus (MRSA) represented 9 (53.0 %) of S.aureus isolates. Constitutive (cMLSb) and inducible clindamycin resistance (iMLSb) phenotypes were detected in 36 (36.0%) and 14 (14,0%) of the isolates, respectively. S. aureus exhibited 38.4% of cMLSb and 13.7% of iMLSb. The result of multivariate analysis showed that age groups, gender, type of samples, provenance, and bacteria, were not significantly associated with Gram-positive cocci iMLSb phenotype.
Conclusion. The study reported for the first time a high prevalence of inducible resistance of Gram-positive cocci strains to clindamycin in Niger Republic. This suggests the urgent need for the implementation of regular screening of these isolates and the wise use of clindamycin in clinical practice.
Pectobacterium araliae sp. nov., a pathogen causing bacterial soft rot of Japanese angelica tree in Japan
Authors: Sawada Hiroyuki , Someya Nobutaka , Morohoshi Tomohiro , Ono Mitsuaki , Satou Mamoru
Published: April 2024

Phytopathogenic bacteria (MAFF 302110T and MAFF 302107) were isolated from lesions on Japanese angelica trees affected by bacterial soft rot in Yamanashi Prefecture, Japan. The strains were Gram-reaction-negative, facultatively anaerobic, motile with peritrichous flagella, rod-shaped, and non-spore-forming. The genomic DNA G+C content was 51.1 mol % and the predominant cellular fatty acids included summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C16 : 0, summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 2 (comprising any combination of C12 : 0 aldehyde, an unknown fatty acid with an equivalent chain length of 10.928, C16 : 1 iso I, and C14 : 0 3OH), and C12 : 0. Phylogenetic analyses based on 16S rRNA and gyrB gene sequences, along with phylogenomic analysis utilizing whole-genome sequences, consistently placed these strains within the genus Pectobacterium. However, their phylogenetic positions did not align with any known species within the genus. Comparative studies involving average nucleotide identity and digital DNA–DNA hybridization with the closely related species indicated values below the thresholds employed for the prokaryotic species delineation (95–96 % and 70 %, respectively), with the highest values observed for Pectobacterium polonicum DPMP315T (92.10 and 47.1 %, respectively). Phenotypic characteristics, cellular fatty acid composition, and a repertoire of secretion systems could differentiate the strains from their closest relatives. The phenotypic, chemotaxonomic, and genotypic data obtained in this study show that MAFF 302110T/MAFF 302107 represent a novel species of the genus Pectobacterium, for which we propose the name Pectobacterium araliae sp. nov., designating MAFF 302110T (=ICMP 25161T) as the type strain.
Drug company methodologies used for reporting in the UK pharmaceutical industry payment transparency database between 2015-2019: A content analysis
Authors: Larkin James , Matthes Britta , Azribi Mohamed , Kearns Conor , Mulinari Shai , Rickard Emily , Moriarty Frank , Fahey Tom , Ozieranski Piotr
Published: April 2024

Background Pharmaceutical companies make hundreds of millions of pounds in marketing/R&D-related payments annually to healthcare organisations and healthcare professionals. UK pharmaceutical industry self-regulatory bodies require member companies who sign up to their code of conduct to publish details of their payments. They are also required to publish the methodologies underlying these payments - methodological notes. This study aimed to analyse UK pharmaceutical companies' methodological notes and their adherence to the relevant codes of conduct and guidance. Methods We conducted a content analysis of methodological notes for the years 2015, 2017 and 2019 and assessed companies' adherence to self-regulatory bodies' requirements and recommendations for methodology disclosure. Results Overall, 90 companies made payment disclosures in all three years, publishing 269 methodological notes. We found gaps in adherence to self-regulatory requirements. Only 3 (3.3%) companies provided clear information for all self-regulatory body recommendations and regulations in all of their notes. Companies also varied in their approaches to important areas. For example, of the 244 notes with clear information on VAT management, 36.1% (N=88) included VAT, 30.3% (N=74) excluded VAT, and 33.6% (N=82) had multiple rules for VAT. Conclusions There was evidence of widespread non-adherence to self-regulatory requirements. This suggests flaws with self-regulation and a need for greater enforcement of rules or consideration of a publicly mandated disclosure system.
Automated quality control of T1-weighted brain MRI scans for clinical research: methods comparison and design of a quality prediction classifier
Authors: Bhalerao Gaurav , Gillis Grace , Dembele Mohamed , Suri Sana , Ebmeier Klaus , Klein Johannes , Hu Michele , Mackay Clare , Griffanti Ludovica
Published: April 2024

Introduction

T1-weighted MRI is widely used in clinical neuroimaging for studying brain structure and its changes, including those related to neurodegenerative diseases, and as anatomical reference for analysing other modalities. Ensuring high-quality T1-weighted scans is vital as image quality affects reliability of outcome measures. However, visual inspection can be subjective and time-consuming, especially with large datasets. The effectiveness of automated quality control (QC) tools for clinical cohorts remains uncertain. In this study, we used T1w scans from elderly participants within ageing and clinical populations to test the accuracy of existing QC tools with respect to visual QC and to establish a new quality prediction framework for clinical research use.

Methods

Four datasets acquired from multiple scanners and sites were used (N= 2438, 11 sites, 39 scanner manufacturer models, 3 field strengths – 1.5T, 3T, 2.9T, patients and controls, average age 71 ± 8 years). All structural T1w scans were processed with two standard automated QC pipelines (MRIQC and CAT12). The agreement of the accept-reject ratings was compared between the automated pipelines and with visual QC. We then designed a quality prediction framework that combines the QC measures from the existing automated tools and is trained on clinical datasets. We tested the classifier performance using cross-validation on data from all sites together, also examining the performance across diagnostic groups. We then tested the generalisability of our approach when leaving one site out and explored how well our approach generalises to data from a different scanner manufacturer and/or field strength from those used for training.

Results

Our results show significant agreement between automated QC tools and visual QC (Kappa=0.30 with MRIQC predictions; Kappa=0.28 with CAT12’s rating) when considering the entire dataset, but the agreement was highly variable across datasets. Our proposed robust undersampling boost (RUS) classifier achieved 87.7% balanced accuracy on the test data combined from different sites (with 86.6% and 88.3% balanced accuracy on scans from patients and controls respectively). This classifier was also found to be generalisable on different combinations of training and test datasets (leave-one-site-out = 78.2% average balanced accuracy; exploratory models = 77.7% average balanced accuracy).

Conclusion

While existing QC tools may not be robustly applicable to datasets comprised of older adults who have a higher rate of atrophy, they produce quality metrics that can be leveraged to train a more robust quality control classifiers for ageing and clinical cohorts.
Menstrual hygiene management in two districts of Malawi
Authors: Hinton Rebekah G.K. , Tremblay-Lévesque Laurent-Charles , Kanjaye Modesta , Macleod Christopher J.A. , Troldborg Mads , Kalin Robert M.
Published: April 2024

1

Menstrual hygiene management (MHM) forms a critical component of ensuring access to adequate and equitable sanitation for all, as outlined in SDG 6.2. Despite its importance, little is known about MHM in Malawi, particularly at a household level. Through a household survey of MHM within 2 districts, we evaluated the type of menstrual absorbents used by people who menstruate. Reusable cloths/rags were the most used menstrual absorbent, used by 79.5% of respondents, whilst disposable absorbents, such as tampons and sanitary pads, were used by 18.6% of respondents. Appropriate MHM also incorporates adequate management of MHM materials, including the washing and drying of reusable menstrual absorbents. We evaluated the cleaning of reusable menstrual absorbents; most respondents (90.1%) reported appropriate washing of menstrual absorbents using soap and water, however only 20.3% reported that menstrual absorbents were dried outside in the sun (as is best practise) with most reporting that reusable menstrual absorbents were dried inside their homes. Our findings highlight the need for improved MHM within Malawi, not only in the access and affordability of appropriate menstrual absorbents but also the promotion of appropriate washing and drying of menstrual absorbents.
Prevalence of Social Anxiety Disorder and its associated factors among Foreign-born Undergraduate Students in Türkiye: A Cross-Sectional Study
Authors: Alnemr Lujain , Salama Abdelaziz H. , Abdelrazek Salma , Alfakeer Hussein , Ali Alkhateeb Mohamed , Torun Perihan
Published: April 2024

Social anxiety disorder (SAD) is prevalent among university students, yet data on its severity among foreign-born international undergraduate students in Türkiye remains limited. This study aims to determine the prevalence of SAD and its associated factors within this population. A cross-sectional study was conducted using a Google Form survey distributed across various universities from September 17, 2023, to February 1, 2024. The survey comprised two sections: sociodemographic information and 17 items of the Social Phobia Inventory (SPIN), which measures the frequency and intensity of social anxiety symptoms. Data analysis included descriptive statistics and inferential analysis, multiple regression, and binomial logistic regression. Out of 506 participants, 455 were included in the study. Results revealed that 39.1% exhibited no or very mild symptoms of SAD, while 23.7% experienced mild symptoms, 21.3% faced moderate symptoms, and 11.6% and 4.2% presented with severe to very severe symptoms, respectively. Factors such as gender (p < 0.0001), previous academic failures (p = 0.013), family history of mental health issues (p = 0.009), exercise frequency (p < 0.0001), and perceptions of relationships with classmates (p < 0.0001) were significantly associated with SAD. Females showed a higher probability of SAD compared to males (OR = 1.976). Individuals engaging in over 90 minutes of exercise per week were less likely to have SAD (OR = 0.383), and occasional smokers had a lower risk of SAD compared to non-smokers (OR = 0.422). Our study uncovered a notably elevated prevalence of Social Anxiety Disorder (SAD) among foreign-born undergraduate students in Türkiye. Factors such as being female, having a family history of mental illnesses, studying in a stressful environment, experiencing academic failure, and engaging in less frequent exercise were associated with noticeable symptoms of SAD. These findings emphasize the urgent need for heightened efforts in recognizing and addressing SAD within this population.
Spatial Coding Dysfunction and Network Instability in the Aging Medial Entorhinal Cortex
Authors: Herber Charlotte S. , Pratt Karishma J.B. , Shea Jeremy M. , Villeda Saul A. , Giocomo Lisa M.
Published: April 2024

Across species, spatial memory declines with age, possibly reflecting altered hippocampal and medial entorhinal cortex (MEC) function. However, the integrity of cellular and network-level spatial coding in aged MEC is unknown. Here, we leveragedin vivoelectrophysiology to assess MEC function in young, middle-aged, and aged mice navigating virtual environments. In aged grid cells, we observed impaired stabilization of context-specific spatial firing, correlated with spatial memory deficits. Additionally, aged grid networks shifted firing patterns often but with poor alignment to context changes. Aged spatial firing was also unstable in an unchanging environment. In these same mice, we identified 458 genes differentially expressed with age in MEC, 61 of which had expression correlated with spatial firing stability. These genes were enriched among interneurons and related to synaptic transmission. Together, these findings identify coordinated transcriptomic, cellular, and network changes in MEC implicated in impaired spatial memory in aging.
Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats
Authors: Martinez Maricela X. , Alizo Vera Vanessa , Ruiz Christina M. , Floresco Stan B. , Mahler Stephen V.
Published: April 2024

Rationale

Adolescent cannabis use is linked to later-life changes in cognition, learning, and memory. Rodent experimental studies suggest Δ9-tetrahydrocannabinol (THC) influences development of circuits underlying these processes, especially in the prefrontal cortex, which matures during adolescence.

Objective

We determined how 14 daily THC injections (5mg/kg) during adolescence persistently impacts medial prefrontal cortex (mPFC) dopamine-dependent cognition.

Methods

In adult Long Evans rats treated as adolescents with THC (AdoTHC), we quantify performance on two mPFC dopamine-dependent reward-based tasks—strategy set shifting and probabilistic discounting. We also determined how acute dopamine augmentation with amphetamine (0, 0.25, 0.5 mg/kg), or specific chemogenetic stimulation of ventral tegmental area (VTA) dopamine neurons and their projections to mPFC impacts probabilistic discounting.

Results

AdoTHC sex-dependently impacts acquisition of cue-guided instrumental reward seeking, but has minimal effects on set-shifting or probabilistic discounting in either sex. When we challenged dopamine circuits acutely with amphetamine during probabilistic discounting, we found reduced discounting of improbable reward options, with AdoTHC rats being more sensitive to these effects than controls. In contrast, neither acute chemogenetic stimulation of VTA dopamine neurons nor pathway-specific chemogenetic stimulation of their projection to mPFC impacted probabilistic discounting in control rats, although stimulation of this cortical dopamine projection slightly disrupted choices in AdoTHC rats.

Conclusions

These studies confirm a marked specificity in the cognitive processes impacted by AdoTHC exposure. They also suggest that some persistent AdoTHC effects may alter amphetamine-induced cognitive changes in a manner independent of VTA dopamine neurons or their projections to mPFC.
Acute myeloid leukemia mitochondria hydrolyze ATP to resist chemotherapy
Authors: Hagen James T , Montgomery Mclane M , Aruleba Raphael T , Chrest Brett R , Green Thomas D , Kassai Miki , Zeczycki Tonya N , Schmidt Cameron A , Bhowmick Debajit , Tan Su-Fern , Feith David J , Chalfant Charles E , Loughran Thomas P , Liles Darla , Minden Mark D , Schimmer Aaron D , Cabot Myles C , Mclung Joseph M , Fisher-Wellman Kelsey H
Published: April 2024

Despite early optimism, therapeutics targeting oxidative phosphorylation (OxPhos) have faced clinical setbacks, stemming from their inability to distinguish healthy from cancerous mitochondria. Herein, we describe an actionable bioenergetic mechanism unique to cancerous mitochondria inside acute myeloid leukemia (AML) cells. Unlike healthy cells which couple respiration to the synthesis of ATP, AML mitochondria were discovered to support inner membrane polarization by consuming ATP. Because matrix ATP consumption allows cells to survive bioenergetic stress, we hypothesized that AML cells may resist cell death induced by OxPhos damaging chemotherapy by reversing the ATP synthase reaction. In support of this, targeted inhibition of BCL-2 with venetoclax abolished OxPhos flux without impacting mitochondrial membrane potential. In surviving AML cells, sustained polarization of the mitochondrial inner membrane was dependent on matrix ATP consumption. Mitochondrial ATP consumption was further enhanced in AML cells made refractory to venetoclax, consequential to downregulations in both the proton-pumping respiratory complexes, as well as the endogenous F1-ATPase inhibitorATP5IF1. In treatment-naive AML,ATP5IF1knockdown was sufficient to drive venetoclax resistance, whileATP5IF1overexpression impaired F1-ATPase activity and heightened sensitivity to venetoclax. Collectively, our data identify matrix ATP consumption as a cancer-cell intrinsic bioenergetic vulnerability actionable in the context of mitochondrial damaging chemotherapy.
Slow kinesin-dependent microtubular transport facilitates ribbon synapse assembly in developing cochlear inner hair cells
Authors: Voorn Roos Anouk , Sternbach Michael , Jarysta Amandine , Rankovic Vladan , Tarchini Basile , Wolf Fred , Vogl Christian
Published: April 2024

Sensory synapses are characterized by electron-dense presynaptic specializations, so-called synaptic ribbons. In cochlear inner hair cells (IHCs), ribbons play an essential role as core active zone (AZ) organizers, where they tether synaptic vesicles, cluster calcium channels and facilitate the temporally-precise release of primed vesicles. While a multitude of studies aimed to elucidate the molecular composition and function of IHC ribbon synapses, the developmental formation of these signalling complexes remains largely elusive to date. To address this shortcoming, we performed long-term live-cell imaging of fluorescently-labelled ribbon precursors in young postnatal IHCs to track ribbon precursor motion. We show that ribbon precursors utilize the apico-basal microtubular (MT) cytoskeleton for targeted trafficking to the presynapse, in a process reminiscent of slow axonal transport in neurons. During translocation, precursor volume regulation is achieved by highly dynamic structural plasticity – characterized by regularly-occurring fusion and fission events. Pharmacological MT destabilization negatively impacted on precursor translocation and attenuated structural plasticity, whereas genetic disruption of the anterograde molecular motor Kif1a impaired ribbon volume accumulation during developmental maturation. Combined, our data thus indicate an essential role of the MT cytoskeleton and Kif1a in adequate ribbon synapse formation and structural maintenance.
Molecular Dynamics Trajectory Analysis of Permeation (MDTAP): A tool to analyze permeation events across membrane proteins
Authors: Raghuvamsi Palur Venkata , Sundaresan Sruthi , Rathinavelan Thenmalarchelvi
Published: April 2024

Background and Objective

Molecular dynamics (MD) simulations are indispensable and versatile in capturing the time-dependent conformational changes of biomolecules to shed light on the concomitant biological processes. MD is used to provide critical mechanistic insights into the transportation of solvent/solute/drug molecules across protein channels embedded in a membrane bilayer. The huge size and volume of the MD trajectories of a membrane-embedded system provide challenges in the analyses of membrane permeation events. Thus, a software, Molecular Dynamics Trajectory Analysis of Permeation (MDTAP), is presented here to analyze the permeation events across membrane-embedded proteins and nucleic acids automatically.

Methods

A software is developed here to automatically detect the permeation events across the channels irrespective of their shape and size and the type of solute molecules from the MD trajectories. MDTAP employs bash scripts to fetch information about the permeation, residence time, and diffusion of the molecules of interest in a Linux/Mac-based environment. The source code of MDTAP is freely available to the public, along with installation and usage information on GitHub (attached as supplementary for the review process and will be made accessible to the public through the following link upon acceptance for publication:https://github.com/MBL-lab/MDTAP).

Results

The efficiency of MDTAP is demonstrated here by considering the MD trajectories of 2 water-conducting channels as test cases:E. coliouter membrane protein Wzi andE. coliAquaporin Z. The dimensions of the channels and their capacity to accommodate and conduct water, the number of permeating water molecules along with the path traced and time taken to cross the channel is validated.

Conclusion

In summary, the graphical representation of the time-dependent behavior of the solute/solvent permeation events corresponding to an MD trajectory in MDTAP allows the user to easily visualize the mechanism of permeation, including the localization of the permeating molecule (if any) and permeating path. Thus, MDTAP immensely reduces the difficult task of manually analyzing solute/solvent permeations from the bulk MD trajectories. Such a simplistic representation of permeation events across the protein transporters helps in the design of drug molecules to treat the associated diseases. Further, MDTAP is also designed to characterize the permeation events across artificial nucleic acid channels, considering their importance in recent times.
Bringing PanglaoDB to 5-star Linked Open Data using Wikidata
Authors: Lubiana Tiago , Cavalcante João Vitor F.
Published: April 2024

PanglaoDB is a database of cell-type markers widely used for single-cell RNA sequencing data analysis. However, cell types and genes in the database are encoded by free text, lacking proper identifiers. Wikidata, is a freely editable knowledge graph database useful for integrating biomedical knowledge. We thus reasoned that porting PanglaoDB’s markers to the platform could improve their reusability and overall technical quality (FAIRness).

We mapped 188 cell types from PanglaoDB to species-neutral terms on Wikidata and created 376 species-specific terms for cell types inHomo sapiensandMus musculus. These terms were enriched with marker information via thehas marker(P8872) property, totaling over 15.000 cell type X marker associations (w.wiki/9iw6). We explored this new subset of the graph via SPARQL queries, illustrating the discovery potential of structured, integrated knowledge. For example, we found a previously unexplored link between rosehip neurons, clozapine, and schizophrenia via theHRH1marker. Besides the graph-based insights, we took time to describe the details of the reconciliation process, hoping to stimulate more resources for a move to a 5-star linked open data format.
Robust self-supervised denoising of voltage imaging data using CellMincer
Authors: Wang Brice , Ma Tianle , Chen Theresa , Nguyen Trinh , Crouse Ethan , Fleming Stephen J. , Walker Alison S. , Valakh Vera , Nehme Ralda , Miller Evan W. , Farhi Samouil L. , Babadi Mehrtash
Published: April 2024

Voltage imaging enables high-throughput investigation of neuronal activity, yet its utility is often constrained by a low signal-to-noise ratio (SNR). Conventional denoising algorithms, such as those based on matrix factorization, impose limiting assumptions about the noise process and the spatiotemporal structure of the signal. While deep learning based denoising techniques offer greater adaptability, existing approaches fail to fully exploit the fast temporal dynamics and unique short- and long-range dependencies within voltage imaging datasets. Here, we introduce CellMincer, a novel self-supervised deep learning method designed specifically for denoising voltage imaging datasets. CellMincer operates on the principle of masking and predicting sparse sets of pixels across short temporal windows and conditions the denoiser on precomputed spatiotemporal auto-correlations to effectively model long-range dependencies without the need for large temporal denoising contexts. We develop and utilize a physics-based simulation framework to generate realistic datasets for rigorous hyperparameter optimization and ablation studies, highlighting the key role of conditioning the denoiser on precomputed spatiotemporal auto-correlations to achieve 3-fold further reduction in noise. Comprehensive benchmarking on both simulated and real voltage imaging datasets, including those with paired patch-clamp electrophysiology (EP) as ground truth, demonstrates CellMincer’s state-of-the-art performance. It achieves substantial noise reduction across the entire frequency spectrum, enhanced detection of subthreshold events, and superior cross-correlation with ground-truth EP recordings. Finally, we demonstrate how CellMincer’s addition to a typical voltage imaging data analysis workflow improves neuronal segmentation, peak detection, and ultimately leads to significantly enhanced separation of functional phenotypes.
Associations between SARS-CoV-2 Infection or COVID-19 Vaccination and Human Milk Composition: A Multi-Omics Approach
Authors: Couvillion Sneha , Nakayasu Ernesto S. , Webb-Robertson Bobbie-Jo M. , Yang Isabella , Eder Josie , Nicora Carrie D. , Bramer Lisa M. , Gao Yuqian , Fox Alisa , DeCarlo Claire , Yang Xiaoqi , Zhou Mowei , Pace Ryan M. , Williams Janet E. , McGuire Mark A. , McGuire Michelle K. , Metz Thomas O. , Powell Rebecca L.
Published: April 2024

The risk of contracting SARS-CoV-2 via human milk-feeding is virtually non-existent. Adverse effects of COVID-19 vaccination for lactating individuals are not different from the general population, and no evidence has been found that their infants exhibit adverse effects. Yet, there remains substantial hesitation among this population globally regarding the safety of these vaccines. Herein we aimed to determine if compositional changes in milk occur following infection or vaccination, including any evidence of vaccine components. Using an extensive multi-omics approach, we found that compared to unvaccinated individuals SARS-CoV-2 infection was associated with significant compositional differences in 67 proteins, 385 lipids, and 13 metabolites. In contrast, COVID-19 vaccination was not associated with any changes in lipids or metabolites, although it was associated with changes in 13 or fewer proteins. Compositional changes in milk differed by vaccine. Changes following vaccination were greatest after 1-6 hours for the mRNA-based Moderna vaccine (8 changed proteins), 3 days for the mRNA-based Pfizer (4 changed proteins), and adenovirus-based Johnson and Johnson (13 changed proteins) vaccines. Proteins that changed after both natural infection and Johnson and Johnson vaccine were associated mainly with systemic inflammatory responses. In addition, no vaccine components were detected in any milk sample. Together, our data provide evidence of only minimal changes in milk composition due to COVID-19 vaccination, with much greater changes after natural SARS-CoV-2 infection.

IMPORTANCE

The impact of the observed changes in global milk composition on infant health remain unknown. These findings emphasize the importance of vaccinating the lactating population against COVID-19, as compositional changes in milk were found to be far less evident after vaccination compared to SARS-CoV-2 infection. Importantly, vaccine components were not detected in milk after vaccination.
Linear infrastructure drives biotic homogenization among bird species of a tropical dry forest
Authors: Hewavithana Dishane K , Weerakoon Devaka K , Wijesinghe Mayuri R , Searcy Christopher A
Published: April 2024

Linear infrastructures (LIs) such as roads, railroads, and powerlines are expanding rapidly around the globe. While most future developments are projected to take place in tropical regions, available information on impacts of LIs is biased towards single species studies of solely road impacts in temperate regions. Therefore, we investigated impacts of three types of LIs (road, railroad, and powerline) on the bird community of a tropical dry forest. Point-count surveys to record avian richness and abundance were conducted at 80 plots that were spatially stratified to include sites proximate to all possible LI combinations. Five measures of vegetation structure were collected at each plot as well. We then assessed the relationship between the bird community (i.e., richness, abundance, composition) and distance to each LI type while accounting for variation in vegetation structure. Species richness and abundance both declined significantly (25% and 20%, respectively) from edge habitat next to railroad to interior forest plots, while community composition was significantly altered by the distance to all three LIs. Road and railroad (both forms of dynamic infrastructure with moving vehicles) had similar effects on the bird community that contrasted with those of powerline (a type of static infrastructure). The resulting ordination reveled that Sri Lankan endemics are significantly disfavored by LI proximity, while the three species most often found proximal to LIs all have naturalized populations across the world. Our results emphasize that LI drive biotic homogenization by favoring generalist species at the expense of unique elements of the biota.
Spatial chemistry of citrus reveals molecules bactericidal toCandidatusLiberibacter asiaticus
Authors: Aksenov Alexander A. , Blacutt Alex , Ginnan Nichole , Rolshausen Philippe E. , Melnik Alexey V. , Lotfi Ali , Gentry Emily C. , Ramasamy Manikandan , Zuniga Cristal , Zengler Karsten , Mandadi Kranthi , Dorrestein Pieter C. , Roper Caroline
Published: April 2024

Huanglongbing (HLB), associated with the psyllid-vectored phloem-limited bacterium,CandidatusLiberibacter asiaticus(CLas), is a disease threat to all citrus production worldwide. Currently, there are no sustainable curative or prophylactic treatments available. In this study, we utilized mass spectrometry (MS)-based metabolomics in combination with 3D molecular mapping to visualize complex chemistries within plant tissues to explore how these chemistries changein vivoin HLB-impacted trees. We demonstrate how spatial information from molecular maps of branches and single leaves yields insight into the biology not accessible otherwise. In particular, we found evidence that flavonoid biosynthesis is disrupted in HLB-impacted trees, and an increase in the polyamine, feruloylputrescine, is highly correlated with an increase in disease severity. Based on mechanistic details revealed by these molecular maps, followed by metabolic modeling, we formulated and tested the hypothesis thatCLas infection either directly or indirectly converts the precursor compound, ferulic acid, to feruloylputrescine to suppress the antimicrobial effects of ferulic acid and biosynthetically downstream flavonoids. Usingin vitrobioassays, we demonstrated that ferulic acid and bioflavonoids are indeed highly bactericidal toCLas, with the activity on par with a reference antibiotic, oxytetracycline, recently approved for HLB management. We propose these compounds should be evaluated as therapeutics alternatives to the antibiotics for HLB treatment. Overall, the utilized 3D metabolic mapping approach provides a promising methodological framework to identify pathogen-specific inhibitory compoundsin plantafor potential prophylactic or therapeutic applications.
Real-time Taxonomic Characterization of Long-read Mixed-species Sequencing Samples in Sorted Motif Distance Space:Voyager
Authors: Branders Sverre , Grabherr Manfred G. , Ahmad Rafi
Published: April 2024

Recent advances in long-read sequencing technology enable its use in potentially life-saving applications for rapid clinical diagnostics and epidemiological monitoring. To take advantage of these enabling characteristics, we presentVoyager, a novel algorithm that complements real-time sequencing by rapidly and efficiently mapping long sequencing reads with insertion- and deletion errors to a large set of reference genomes. The concept ofSorted Motif Distance Space(SMDS), i.e., distances between exact matches of short motifs sorted by rank, represents sequences and sequence complementarity in a highly compressed form and is thus computationally efficient while enabling strain-level discrimination. In addition,Voyagerapplies a deconvolution algorithm rather than reducing taxonomic resolution if sequences of closely related organisms cannot be discerned bySMDSalone. Using relevant real-world data, we evaluatedVoyageragainst the current best taxonomic classification methods (Kraken 2 and Centrifuge).Voyagerwas on average more than twice as fast as the current fastest method and obtained on average over 40% higher species level accuracy while maintaining lower memory usage than both other methods.
A multistate capture-recapture model to estimate reproduction of North Atlantic right whales
Authors: Linden Daniel W. , Pace Richard M. , Garrison Lance P. , Hostetler Jeffrey A. , Knowlton Amy R. , Lesage Véronique , Williams Rob , Runge Michael C.
Published: April 2024

The recent steep decline of critically endangered North Atlantic right whales (Eubalaena glacialis) can be attributed to high mortality combined with low reproduction. While the former is a clear result of anthro-pogenic activity, the latter involves more complexity. Evidence suggests that both short-term fluctuations in prey availability and long-term decline in health are responsible for depressed right whale calving rates. To facilitate an assessment of extinction risk, we developed a multistate capture-recapture model that estimated the probability of calving using extensive sightings data from 1990-2019. The model estimated sub-lethal effects of severe injury on calving probability, and modeled temporal variability in calving as related to indices of prey availability (Calanusspp. biomass) and an apparent regime shift. The average annual probability of calving for known-breeding females, given average prey conditions, decreased from 0.217 [0.162, 0.281] to 0.142 [0.067, 0.252] after the 2010 regime shift. The model indicated strong evidence of a relationship between calving probability and the prey index from the eastern Gulf of Maine, though this relationship effectively disappeared after 2010; moderate evidence for a relationship with prey from the southwest Gulf of St. Lawrence remained. Weak evidence of reduced calving probability due to severe injury resulted from low sample sizes, given increased mortality for individuals observed with severe injuries. The regime effect is hypothesized to be capturing a long-term decline in health due to a combination of decreasing habitat quality resulting from climate change and potentially chronic sublethal injuries (e.g., entanglements). Our reproduction model provides demographic parameter estimates that can be used in population projections for North Atlantic right whales, though uncertainty remains in the mechanisms responsible for recent declines in calving.
The Development of a Brain Injury Survivor Patient and Public Involvement Group by a Brain Injury Survivor
Authors: Piercy James , Hamilton Colin , Runcie Robert , Deaton Christi , Joannides Alexis J
Published: April 2024

Background

Patient and public involvement (PPI) in research is seen as key to ensuring applicability and impact. Undertaking PPI in people after brain injury has long been seen to be a challenge. In 2020 The NIHR Brain Injury MedTech Cooperative developed a programme with the aim of improving PPI involvement, impact and diversity in this population.

Methods

Through a process of iterative development, a PPI programme was created. It built on an existing underutilised database of people after brain injury and their carers who were interested in engaging with PPI and utilised video-calling software. It was led by a Brain injury Survivor acting as Facilitator with admin support from the MedTech Cooperative.

Results

To date 14 PPI sessions were completed supporting a total of 17 projects. The diversity of the panel members was comparable to that of the population at large. However, further work is needed, especially in engaging people experiencing homelessness, people living outside of England and those with communication impairments. Feedback from researchers was positive and specific impacts are stated.

Conclusion

Through the leadership of a facilitator who has an understanding of the lived experience of brain injury a PPI programme has been developed. The use of a video-calling platform enabled a wider representation then a face-to-face group would have and techniques such as shortened sessions and single project presentations ensured engagement and impact.
Systematic Discovery of Phage Genes that Inactivate Bacterial Immune Systems
Authors: Ojima Shinjiro , Azam Aa Haeruman , Kondo Kohei , Nie Wenhan , Wang Sai , Chihara Kotaro , Tamura Azumi , Yamashita Wakana , Nakamura Tomohiro , Sugawara Yo , Sugai Motoyuki , Zhu Bo , Takahashi Yoshimasa , Watashi Koichi , Kiga Kotaro
Published: April 2024

Bacteria have developed numerous defense systems to counter phage infections. However, the extent to which phages possess countermeasures against these defense systems remains unclear. In this study, we combined a phage gene knockout library with a defense system library to analyze the mechanisms by which phages counteract bacterial defense systems. After attempting gene deletions of 105 open reading frames (ORFs) in the DruSM1 phage (ΦDruSM1), we successfully generated 73 different ORF knockout phages. By infecting this library with bacteria harboring defense system expression plasmids, we identified inactivators of Druantia type I (Druad1), Brex type I, AVAST type III, Sir2+HerA, DUF4297+HerA, and hhe, as well as an activator of Retron Ec86, in a single phage genome. Synthetic phages incorporating Druad1 effectively eradicatedEscherichia coliharboring the robust Druantia type I defense system by altering DNA methylation at m6A sites of the phage. This study highlighted the prevalence of various antidefense mechanisms employed by phages to overcome bacterial defense systems.
Deciphering the complex interplay between physical activity, inflammatory bowel disease and obesity/BMl through causal inference and mediation analyses
Authors: Lian Wensuo , Zhao Yuhui , Li Hongxia , Jia Linlin , Yao Kaixin , Li Nan , He Yuxin
Published: April 2024

This study investigated the causal effect of physical activity (PA) on inflammatory bowel disease (IBD) and the role of body mass index (BMI) as a mediator. We used instrumental variables for moderate to vigorous physical activity (MVPA) during leisure time and leisure screen time (LST) derived from genome-wide association studies (GWASs) meta-analysis. IBD, Crohn’s disease (CD), and ulcerative colitis (UC) summary statistics were sourced from GWASs on European populations. We conducted univariable Mendelian randomization (UVMR) to assess the direct impacts of MVPA and LST on IBD risk. Multivariable Mendelian randomization (MVMR) was used to evaluate the mediating effects of BMI. Results indicated a protective effect of MVPA against IBD and CD. Conversely, higher genetically-predicted LST correlated with increased IBD and CD risks. BMI mediated 0.8% and 3.7% of the LST effect on IBD/CD, respectively, and 3.5% and 11.0% of the MVPA effect. Thus, PA appears causally related to lower IBD/CD risk, with BMI partially mediating this relationship, highlighting the risk increase from reduced PA via elevated BMI.

Key messages

What is already known?

Observational studies have shown that occupations involving more physical labor are associated with a lower risk of IBD compared with sedentary occupations.

What is new here?

The causal effect of PA on IBD and the role of BMI as a mediator between PA and IBD were investigated.

How can this study help patient care?

The incidence of CD can be reduced by promoting lifestyle management, such as reducing recreational sedentary activities and encouraging proper exercise. In addition, individuals who are not physically active should monitor their BMI to prevent the development of CD.
Vestibular rehabilitation practice in neurorehabilitation: an Italian survey protocol
Authors: Ferri Nicola , Piermaria Jacopo , Manzari Leonardo , Turolla Andrea , Morone Giovanni , Tramontano Marco
Published: April 2024

Introduction

Neurological disorders are a prevalent cause of disability and death, which has a considerable impact on the world’s economic and healthcare systems, not least because of rehabilitation needs. Neurorehabilitation is effective and recommended for the best recovery of motor and cognitive functions and quality of life. This study evaluates clinicians’ perceptions of vestibular rehabilitation’s actual or potential role in neurorehabilitation.

Methods

This is the protocol for a cross-sectional study that will be conducted as an online survey approved by the University of Bologna Bioethics Committee. The survey lasts approximately 10 minutes and consists of 4 main sections (socio-demographic, professional, clinical, and future recommendation data), with a total of 27 closed questions and 2 open questions. 5 experts constructed the questionnaire, and then 6 respondents piloted it; these latter were representative of the subjects to whom it will be administered. We will report the Survey following the Checklist for Reporting Of Survey Studies (CROSS).

Expected results

This questionnaire will map the knowledge and use of vestibular rehabilitation in neurorehabilitation by healthcare professionals in Italy. It will also be useful to assess gaps, challenges, and research perspectives on this prevalent topic.
Metabolic interactions underpinning high methane fluxes across terrestrial freshwater wetlands
Authors: Bechtold Emily K , Ellenbogen Jared B , Villa Jorge A , de Melo Ferreira Djennyfer K , Oliverio Angela M , Kostka Joel E. , Rich Virginia I. , Varner Ruth K , Bansal Sheel , Ward Eric J , Bohrer Gil , Borton Mikayla A , Wrighton Kelly C , Wilkins Michael J
Published: April 2024

Current estimates of wetland contributions to the global methane budget carry high uncertainty, particularly in accurately predicting emissions from high methane-emitting wetlands. Microorganisms mediate methane cycling, yet knowledge of their conservation across wetlands remains scarce. To address this, we integrated 1,118 16S rRNA amplicon datasets (116 new), 305 metagenomes (20 new) that yielded 4,745 medium and high-quality metagenome assembled genomes (MAGs; 617 new), 133 metatranscriptomes, and annual methane flux data across 9 wetlands to create the Multi-Omics for Understanding Climate Change (MUCC) v2.0.0 database. This new resource was leveraged to link microbiome compositional profiles to encoded functions and emissions, with specific focus on methane-cycling populations and the microbial carbon decomposition networks that fuel them. We identified eight methane-cycling genera that were conserved across wetlands, and deciphered wetland specific metabolic interactions across marshes, revealing low methanogen-methanotroph connectivity in high-emitting wetlands. Methanoregula emerged as a hub methanogen across networks and was a strong predictor of methane flux, demonstrating the potential broad relevance of methylotrophic methanogenesis in these ecosystems. Collectively, our findings illuminate trends between microbial decomposition networks and methane flux and provide an extensive publicly available database to advance future wetland research.