bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractVoltage 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

ABSTRACTThe 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.IMPORTANCEThe 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

AbstractLinear 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

AbstractHuanglongbing (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

AbstractRecent 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

AbstractThe 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

AbstractBackgroundPatient 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.MethodsThrough 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.ResultsTo 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.ConclusionThrough 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

SUMMARYBacteria 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

AbstractThis 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 messagesWhat 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

AbstractIntroductionNeurological 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.MethodsThis 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 resultsThis 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.
Genetic and anatomical determinants of olfaction in dogs and wild canids
Authors: Mouton Alice , Bird Deborah , Li Gang , Craven Brent A. , Levine Jonathan M. , Morselli Marco , Pellegrini Matteo , Van Valkenburgh Blaire , Wayne Robert K. , Murphy William J. 
Published: April 2024

AbstractUnderstanding the anatomical and genetic basis of complex phenotypic traits has long been a challenge for biological research. Domestic dogs offer a compelling model as they demonstrate more phenotypic variation than any other vertebrate species. Dogs have been intensely selected for specific traits and abilities, directly or indirectly, over the past 15,000 years since their initial domestication from the gray wolf. Because olfaction plays a central role in critical tasks, such as the detection of drugs, diseases, and explosives, as well as human rescue, we compared relative olfactory capacity across dog breeds and assessed changes to the canine olfactory system resulting from domestication. We conducted a cross-disciplinary survey of olfactory anatomy, olfactory receptor (OR) gene variation, and OR gene expression in domestic dogs. Through comparisons to their closest wild canid relatives, the gray wolf and coyote, we show that domestic dogs might have lost functional OR genes commensurate with a documented reduction in nasal morphology during domestication. Critically, within domestic dogs alone, we found no genetic or morphological profile shared among functional or genealogical breed groupings, such as scent hounds, that might indicate evidence of any human-directed selection for enhanced olfaction. Instead, our results suggest that superior scent detection dogs likely owe their success to advantageous behavioral traits and training rather than an “olfactory edge” provided by morphology or genes.
Subcellular, biochemical and biophysical alterations in two glial cell models of ARSACS
Authors: Murtinheira Fernanda , Boasinha Ana Sofia , Belo João , Macedo Luana , Farsetti Elisa , Robalo Tiago T. , Torres Vukosava M. , Pinto Francisco R. , Fernandes Adelaide , Nascimento Patricia , Rodrigues Mario S. , Herrera Federico 
Published: April 2024

AbstractAutosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a developmental and degenerative disorder caused by loss-of-function mutations in the gene that codifies for the sacsin chaperone. Sacsin was initially described as a neuronal protein but is found in various cell types, including astroglial, microglial, kidney, and skin cell lines. We and others have shown that virtually all cell and animal models of ARSACS show disruption of intermediate filament (IF) cytoskeleton and organelle distribution. This article extends previous observations from our lab on the C6 astroglial-like model and describes the development and characterization of a new human microglial cell model based on HMC3 cells. HMC3 cells knocked out for sacsin show similar alterations to C6 astroglial-like cells: aberrant distribution of IF network and organelles, downregulation of developmental transcription factors STAT3 and Smad1, and alterations in autophagy machinery and markers of intracellular stress, resulting in morphological changes. Our results extend previous observations suggesting a possible role for glial cells in ARSACS and provide new tools to understand the glial-specific mechanisms involved in this pathology.