bluuebunny/crossref_metadata_2025 huggingface dataset:
Where’s Whaledo: A software toolkit for array localization of animal vocalizations
Authors: Snyder Eric R. , Solsona-Berga Alba , Baumann-Pickering Simone , Frasier Kait E. , Wiggins Sean M. , Hildebrand John A.
Published: August 2023

Where’s Whaledois a software toolkit that uses a combination of automated processes and user interfaces to greatly accelerate the process of reconstructing animal tracks from arrays of passive acoustic recording devices. Passive acoustic localization is a non-invasive yet powerful way to contribute to species conservation. By tracking animals through their acoustic signals, important information on diving patterns, movement behavior, habitat use, and feeding dynamics can be obtained. This method is useful for helping to estimate population density, observe behavioral responses to noise, and develop potential mitigation strategies. Animal tracking using passive acoustic localization requires an acoustic array to detect signals of interest, associate detections on various receivers, and estimate the most likely source location by using the time difference of arrival (TDOA) of sounds on multiple receivers.Where’s Whaledocombines data from two small-aperture volumetric arrays and a variable number of individual receivers. In a case study conducted in the Tanner Basin off Southern California, we demonstrate the effectiveness ofWhere’s Whaledoin localizing groups of Cuvier’s beaked whales (Ziphius cavirostris). We reconstruct the tracks of six individual animals vocalizing concurrently and identifyZiphius cavirostristracks despite being obscured by a large pod of vocalizing dolphins.

Author summary

Reconstructing the movement of animals from their vocalizations is a powerful method to observe their behavior in situations where visual monitoring is impractical. Arrays of acoustic recording devices can be used to determine the location of vocalizing animals and a series of locations can be linked to form tracks. However, reconstructing tracks requires methods of determining which animal in a group is vocalizing, finding the same vocalization on multiple recording devices, and determining the most likely location of the animal based on the relative times the sound arrived at various recording devices. We have developed a toolkit calledWhere’s Whaledoto assist researchers in reconstructing the behavior of these animals using arrays of acoustic recording devices. This toolkit greatly accelerates the process of reconstructing their tracks using a combination of automated processes and user interfaces. We useWhere’s Whaledoto reconstruct the tracks of deep-diving Cuvier’s beaked whales. We successfully reconstruct tracks of groups of up to six whales vocalizing concurrently.
An Interpretable Framework to Characterize Compound Treatments on Filamentous Fungi using Cell Painting and Deep Metric Learning
Authors: Lejeune Laurent , Roussin Morgane , Leggio Bruno , Vernay Aurelia
Published: August 2023

The cell painting microscopy imaging protocol has recently gained traction in the biology community as it allows, through the addition of fluorescent dyes, to acquire images that highlight intra-cellular components that are not visible through traditional whole-cell microscopy. While previous works have successfully applied cell painting to mammalian cells, we devise a staining protocol applicable to a filamentous fungus model. Following a principled visual inspection and annotation protocol of phenotypes by domain-experts, we devise an efficient, robust, and conceptually simple image analysis strategy based on the Deep Cosine Metric Learning paradigm that allows to estimate phenotypical similarities across different imaging modalities. We experimentally demonstrate the benefits of our pipeline in the tasks of estimating dose-response curves over a wide range of subtle phenotypical variations. Last, we showcase how our learned metrics can group image samples according to different modes of action and biological targets in an interpretable manner.
Situating the oxytocin receptor gene polymorphisms in the context of structural and connectome-level substrates and association with endogenous oxytocin
Authors: Kaya Kutlu , Önal Deniz , Kartal Yasemin , Budak Murat Timur , Karabulut Erdem , Karlı Oğuz Kader , Pehlivanoğlu Bilge
Published: August 2023

Genetic variants in the oxytocin receptor (OXTR) have been linked to individual differences in social behavior, while aberrant oxytocin regulation is associated with increased susceptibility to neuropsychiatric disorders. Recent magnetic resonance imaging (MRI) studies have demonstrated altered brain morphology and connectivity in response to OXTR single nucleotide polymorphisms (SNP) of GG homozygous compared to targeted allele carriers, such as T or A. However, the sex-specific differences in the structural and connectome-level substrates of OXTR genetic variants and their relationship with endogenous oxytocin remain poorly understood. Therefore, we aimed to decompose structural MRI and functional/structural connectivity to identify sex-specific differences among young adults through OXTR SNPs (rs53576, rs1042778, and rs2254298). High-resolution 3D T1-weighted, resting-state functional, and diffusion tensor images were acquired by sixty-one participants who provided blood samples for quantification of endogenous oxytocin concentrations and use for genotyping, followed by grouping with respect to homozygous and targeted allele carriers. We found that men had greater cortical surface area and sub(cortical) gray matter volume in different homozygous and targeted allele carriers. Resting-state functional and structural connectivity (rsFC and SC, respectively) were allocated differently, primarily in temporal and subcortical brain regions. There were also significant sex-specific differences in mean correlations between endogenous oxytocin and SC, whereas rsFC delineated more significant correlations on the node level. Our results provide valuable insights into sex-specific differences in the structural and connectome-level substrates of OXTR SNPs, contributing to understanding the role of oxytocin in socio-emotional processing and highlighting sex-specific differences in genetic and neural mechanisms underlying social behavior.
Dynamics of bacterial operons during genome-wide stresses
Authors: Jagadeesan Rahul , Dash Suchintak , Palma Cristina S.D. , Baptista Ines S.C. , Chauhan Vatsala , Mäkelä Jarno , Ribeiro Andre S.
Published: August 2023

Bacterial gene networks have many operons, each coordinating the kinetics of a few genes in time and strength. InEscherichia coli, nearly half of these operons have internal promoters, which allow regulating the downstream genes, independently from upstream genes. We studied their role during genome-wide stresses targeting a few key elements of the transcription machinery, namely, RNAP and gyrase. We show that absolute differences in response strength between genes in the same operon follow a sinusoidal function of the distance between them. This results from the combined effect of elongation fall-offs and internal promoters. The frequency of this function is regulated by the positioning of internal promoters, while its amplitude differs with the perturbation strength. Moreover, we find that positive supercoiling buildup partially explains the RNAP fall-off rates. Finally, we report similar sinusoidal patterns inE. colicells subject to several other stresses, as well as inBacillus subtilis, Corynebacterium glutamicum, and Helicobacter pylori. Overall, our results suggest that the strength, number, and positioning of internal promoters in operons are influenced by a genome-wide need to compensate for RNAP fall-offs, and thus provide distal genes in the operon with similar response strength as genes proximal to the primary promoter.
Patient-specific logical models replicate phenotype responses to psoriatic and anti-psoriatic stimuli
Authors: Tsirvouli Eirini , Aker Eir , Kuiper Martin
Published: August 2023

Psoriasis is a dermatologic disease that affects 2% of the world population. Psoriasis is characterized by chronic inflammation and aberrant behavior of keratinocytes, which display increased levels of proliferation, and decreased differentiation and apoptosis. Stimulation of keratinocytes by psoriatic cytokines leads to the increased production of immunostimulatory ligands that further attract immune cells and amplify inflammatory responses. Psoriasis can have severe, moderate, or mild outcomes and while these severity levels demand custom medical treatment schemes, assigning an effective treatment to patients with moderate or severe disease is a demanding task.

The varied responses of patients to treatments highlight a large disease complexity, demanding that new ways to analyze and integrate patients’ molecular profiles are developed to design patient-specific therapies. We have used gene expression values from psoriasis biopsies to separate patients into two clusters, each with distinct expression profiles, but nevertheless not correlating with any of the available clinical data, such as disease severity. When using these gene expression levels in logical model simulations these data became highly descriptive of patient-specific phenotype characteristics. Starting from a psoriatic keratinocyte model that we published recently, we added additional pathways highlighted by a differential gene expression analysis between the subgroups. This included components from the Interleukin-1 family, IFN-alpha/beta and IL-6 signaling pathways. Model personalization was performed by using patient gene expression levels in model configurations, exploiting the PROFILE pipeline. Personalized simulations revealed that the two patient clusters represent more innate immunity-driven, highly inflammatory phenotypes and adaptive immunity-driven, chronic phenotypes, respectively. The model was also able to finely capture differences between responses in patients with a known disease severity. A treatment response analysis among the patient cohort predicted differential responses to the inhibition of psoriatic stimuli, with IL-17, TNFα and PGE2 inhibition reducing proliferation and inflammatory phenotypes. Alternative treatment with PGE2 or TNFα inhibition instead of IL-17 was suggested for patients with high NF-κB activity and prosurvival factors, such as CREB1. With this project, we aim to highlight the value of combining omics data with logical modeling for the detection of ‘emergent’ phenotypes and for gaining disease knowledge on the individual patient level.
Numerical investigation of heterogeneous soft particle pairs in inertial microfluidics
Authors: Owen Benjamin , Thota Krishnaveni , Krüger Timm
Published: August 2023

The formation of pairs of particles or cells of different types in microfluidic channels can be desired or detrimental in healthcare applications. It is still unclear what role softness heterogeneity plays in the formation of these particle pairs. We use an in-house lattice-Boltzmann-immersed-boundary-finite-element solver to simulate a pair of particles with different softness flowing through a straight channel with a rectangular cross-section under initial conditions representative of a dilute suspension. We find that softness heterogeneity significantly affects the pair dynamics, determining whether a pair will form or not, and determining the lateral and inter-particle equilibrium behaviour in the pair. We also observe close matches between the transient deformation of particles in a linear pair and single particles in isolation. These results further our understanding of pair behaviour, providing a foundation for understanding particle train formation, and open up the potential to develop reduced-order models for particle pair formation based upon the behaviour of single particles.
Specialized structure of neural population codes in parietal cortex outputs
Authors: Safaai Houman , Wang Alice Y. , Kira Shinichiro , Malerba Simone Blanco , Panzeri Stefano , Harvey Christopher D.
Published: August 2023

Do cortical neurons that send axonal projections to the same target area form specialized population codes for transmitting information? We used calcium imaging in mouse posterior parietal cortex (PPC), retrograde labeling, and statistical multivariate models to address this question during a delayed match-to-sample task. We found that PPC broadcasts sensory, choice, and locomotion signals widely, but sensory information is enriched in the output to anterior cingulate cortex. Neurons projecting to the same area have elevated pairwise activity correlations. These correlations are structured as information-limiting and information-enhancing interaction networks that collectively enhance information levels. This network structure is unique to sub-populations projecting to the same target and strikingly absent in surrounding neural populations with unidentified projections. Furthermore, this structure is only present when mice make correct, but not incorrect, behavioral choices. Therefore, cortical neurons comprising an output pathway form uniquely structured population codes that enhance information transmission to guide accurate behavior.
Rescue ofMycobacterium bovisDNA obtained from cultured strains during official surveillance of animal TB: key steps for robust whole genome sequence data generation
Authors: Pinto Daniela , Themudo Gonçalo , Pereira André C. , Botelho Ana , Cunha Mónica V.
Published: August 2023

Epidemiological surveillance of animal tuberculosis (TB) based on whole genome sequencing (WGS) ofMycobacterium bovishas recently gained track due to its high resolution to identify infection sources, characterize the pathogen population structure, and for contact tracing. However, the workflow from bacterial isolation to sequence data analyses has several technical challenges that may severely impact the power to understand the epidemiological scenario and inform outbreak response.

While trying to use archived DNA from cultured strains obtained during routine official surveillance of animal TB in Portugal, we struggled against three major challenges: the low amount ofM. bovisDNA obtained from routinely processed animal samples; the lack of purity ofM. bovisDNA,i.e.high levels of contamination with DNA from other organisms; and the co-occurrence of more than oneM. bovisstrain per sample (within-host mixed infection). The loss of an isolate’s genome is a missed link in transmission chain reconstruction, hampering the biological and epidemiological interpretation of data as a whole.

Upon identification of these challenges, we implemented an integrated solution framework, based on whole genome amplification and a dedicated computational pipeline, to minimize their effects and recover as many genomes as possible. With the approaches described herein, we were able to recover 62 out of 100 samples that would have otherwise been lost. Based on these results, we discuss adjustments that should be made in official and research laboratories to facilitate sequential implementation of bacteriological culture, PCR, downstream genomics and computational-based methods. All of this in a time frame supporting data-driven intervention.
Efficient Sequence Embedding For SARS-CoV-2 Variants Classification
Authors: Ali Sarwan , Sardar Usama , Khan Imdad Ullah , Patterson Murray
Published: August 2023

Kernel-based methods, such as Support Vector Machines (SVM), have demonstrated their utility in various machine learning (ML) tasks, including sequence classification. However, these methods face two primary challenges:(i) the computational complexity associated with kernel computation, which involves an exponential time requirement for dot product calculation, and (ii) the scalability issue of storing the largen × nmatrix in memory when the number of data points(n) becomes too large. Although approximate methods can address the computational complexity problem, scalability remains a concern for conventional kernel methods. This paper presents a novel and efficient embedding method that overcomes both the computational and scalability challenges inherent in kernel methods. To address the computational challenge, our approach involves extracting thek-mers/nGrams (consecutive character substrings) from a given biological sequence, computing a sketch of the sequence, and performing dot product calculations using the sketch. By avoiding the need to compute the entire spectrum (frequency count) and operating with low-dimensional vectors (sketches) for sequences instead of the memory-intensiven × nmatrix or full-length spectrum, our method can be readily scaled to handle a large number of sequences, effectively resolving the scalability problem. Furthermore, conventional kernel methods often rely on limited algorithms (e.g., kernel SVM) for underlying ML tasks. In contrast, our proposed fast and alignment-free spectrum method can serve as input for various distance-based (e.g.,k-nearest neighbors) and non-distance-based (e.g., decision tree) ML methods used in classification and clustering tasks. We achieve superior prediction for coronavirus spike/Peplomer using our method on real biological sequences excluding full genomes. Moreover, our proposed method outperforms several state-of-the-art embedding and kernel methods in terms of both predictive performance and computational runtime.
Benchmarking AI-based plasmid annotation tools for antibiotic resistance genes mining from metagenome of the Virilla River, Costa Rica
Authors: Rojas-Villalta Dorian , Calderón-Osorno Melany , Barrantes-Jiménez Kenia , Arias-Andres Maria , Rojas-Jiménez Keilor
Published: August 2023

Bioinformatics and Artificial Intelligence (AI) stand as rapidly evolving tools that have facilitated the annotation of mobile genetic elements (MGEs), enabling the prediction of health risk factors in polluted environments, such as antibiotic resistance genes (ARGs). This study aims to assess the performance of four AI-based plasmid annotation tools (Plasflow, Platon, RFPlasmid, and PlasForest) by employing defined performance parameters for the identification of ARGs in the metagenome of one sediment sample obtained from the Virilla River, Costa Rica. We extracted and sequenced complete DNA from the sample, assembled the metagenome, and then performed the plasmid prediction with each bioinformatic tool, and the ARGs annotation using the Resistance Gene Identifier web portal. Sensitivity, specificity, precision, negative predictive value, accuracy, and F1score were calculated for each ARGs prediction result of the evaluated plasmidomes. Notably, Platon emerged as the highest performer among the assessed tools, exhibiting exceptional scores. Conversely, Plasflow seems to face difficulties distinguishing between chromosomal and plasmid sequences, while PlasForest has encountered limitations when handling small contigs. RFPlasmid displayed diminished specificity and was outperformed by its taxon-dependent workflow. We recommend the adoption of Platon as the preferred bioinformatic tool for resistome investigations in the taxon-independent environmental metagenomic domain. Meanwhile, RFPlasmid presents a compelling choice for taxon-dependent prediction due to its exclusive incorporation of this approach. We expect that the results of this study serve as a guiding resource in selecting AI-based tools for accurately predicting the plasmidome and its associated genes.
Homologous Pairs of Low and High Temperature Originating Proteins Spanning the Known Prokaryotic Universe
Authors: Komp Evan , Alanzi Humood , Francis Ryan , Vuong Chau , Roberts Logan , Mossallenejad Amin , Beck David A. C.
Published: August 2023

Stability of proteins at high temperature has been a topic of interest for many years, as this attribute is favourable for applications ranging from therapeutics to industrial chemical manufacturing. Our current understanding and methods for designing high-temperature stability into target proteins are inadequate. To drive innovation in this space, we have curated a large dataset, learn2thermDB, of protein-temperature examples, totalling 24 million instances, and paired proteins across temperatures based on homology, yielding 69 million protein pairs - orders of magnitude larger than the current largest. This important step of pairing allows for study of high-temperature stability in a sequence-dependent manner in the big data era. The data pipeline is parameterized and open, allowing it to be tuned by downstream users. We further show that the data contains signal for deep learning. This data offers a new doorway towards thermal stability design models.
Evolution of parent-of-origin effects on placental gene expression in house mice
Authors: Rodriguez-Caro Fernando , Moore Emily C. , Good Jeffrey M.
Published: August 2023

The mammalian placenta is a hotspot for the evolution of genomic imprinting, a form of gene regulation that involves the parent-specific epigenetic silencing of one allele. Imprinted genes are central to placental development and are thought to contribute to the evolution of reproductive barriers between species. However, it is unclear how rapidly imprinting evolves or how functional specialization among placental tissues influences the evolution of imprinted expression. We compared parent-of-origin expression bias across functionally distinct placental layers sampled from reciprocal crosses within three closely related lineages of mice (Mus). Using genome-wide gene expression and DNA methylation data from fetal and maternal tissues, we developed an analytical strategy to minimize pervasive bias introduced by maternal contamination of placenta samples. We corroborated imprinted expression at 42 known imprinted genes and identified five candidate imprinted genes showing parent-of-origin specific expression and DNA methylation. Paternally-biased expression was enriched in the labyrinth zone, a layer specialized in nutrient transfer, and maternally-biased genes were enriched in the junctional zone, which specializes in modulation of maternal physiology. Differentially methylated regions were predominantly determined through epigenetic modification of the maternal genome and were associated with both maternally- and paternally-biased gene expression. Lastly, comparisons between lineages revealed a small set of co-regulated genes showing rapid divergence in expression levels and imprinted status in theM. m. domesticuslineage. Together, our results reveal important links between core functional elements of placental biology and the evolution of imprinted gene expression among closely related rodent species.
Temperature and intraspecific variation affect host-parasite interactions
Authors: Ismail Sherine , Farner Johannah , Couper Lisa , Mordecai Erin , Lyberger Kelsey
Published: August 2023

Parasites play key roles in regulating aquatic ecosystems, yet the impact of climate warming on their ecology and disease transmission remains poorly understood. Isolating the effect of warming is challenging as transmission involves multiple interacting species and potential intraspecific variation in temperature responses of one or more of these species. Here, we leverage a wide-ranging mosquito species and its facultative parasite as a model system to investigate the impact of temperature on host-parasite interactions and disease transmission. We conducted a common garden experiment measuring parasite growth and infection rates at seven temperatures using 12 field-collected parasite populations and a single mosquito population. We find that both free-living growth rates and infection rates varied with temperature, which were highest at 18-24.5°C and 13°C, respectively. Further, we find intraspecific variation in peak performance temperature reflecting patterns of local thermal adaptation—parasite populations from warmer source environments typically had higher thermal optima for free-living growth rates. For infection rates, we found a significant interaction between parasite population and nonlinear effects of temperature. These findings underscore the need to consider both host and parasite thermal responses, as well as intraspecific variation in thermal responses, when predicting the impacts of climate change on disease in aquatic ecosystems.
RNA-dependent RNA polymerase of predominant human norovirus forms liquid-liquid phase condensates as viral replication factories
Authors: Kaundal Soni , Anish Ramakrishnan , Ayyar B. Vijayalakshmi , Shanker Sreejesh , Kaur Gundeep , Crawford Sue E. , Pollet Jeroen , Stossi Fabio , Estes Mary K. , Prasad B.V. Venkataram
Published: August 2023

Many viral proteins form biomolecular condensates via liquid-liquid phase separation (LLPS) to support viral replication and evade host antiviral responses, and thus, they are potential targets for designing antivirals. In the case of non-enveloped positive-sense RNA viruses, forming such condensates for viral replication is unclear and less understood. Human noroviruses (HuNoV) are positive-sense RNA viruses that cause epidemic and sporadic gastroenteritis worldwide. Here, we show that the RNA-dependent-RNA polymerase (RdRp) of pandemic GII.4 HuNoV forms distinct condensates that exhibit all the signature properties of LLPS with sustained polymerase activity and the capability of recruiting components essential for viral replication. We show that such condensates are formed in HuNoV-infected human intestinal enteroid cultures and are the sites for genome replication. Our studies demonstrate the formation of phase separated condensates as replication factories in a positive-sense RNA virus, which plausibly is an effective mechanism to dynamically isolate RdRp replicating the genomic RNA from interfering with the ribosomal translation of the same RNA.

Teaser

Polymerase of a positive-sense RNA virus forms LLPS to regulate replication as an elegant solution for an enigmatic question.
Nitrate-driven anaerobic oxidation of ethane and butane by bacteria
Authors: Wu Mengxiong , Li Jie , Lai Chun-Yu , Leu Andy O , Sun Shengjie , Gu Rui , Erler Dirk V , Liu Lian , Li Lin , Tyson Gene W. , Yuan Zhiguo , McIlroy Simon J. , Guo Jianhua
Published: August 2023

The short-chain gaseous alkanes (ethane, propane and butane; SCGAs) are important components of natural gas, yet our understanding of their fate in environmental systems is poorly understood. Microbially mediated anaerobic oxidation of SCGAs coupled to nitrate reduction has been demonstrated for propane, but is yet to be shown for ethane or butane – despite being energetically feasible. Here we report two independent bacterial enrichments performing anaerobic ethane and butane oxidation, respectively, coupled to nitrate reduction to dinitrogen gas and ammonium. Isotopic13C-and15N-labelling experiments, mass and electron balance tests, and metabolite and meta-omics analyses collectively reveal that the recently described propane-oxidising ‘CandidatusAlkanivorans nitratireducens’ was also responsible for nitrate-dependent anaerobic oxidation of the SCGAs in both these enrichments. The complete genome of this species encodes alkylsuccinate synthase genes for the activation of ethane/butane via fumarate addition. Further substrate range tests confirm ‘Ca.A. nitratireducens’ is metabolically versatile, being able to degrade ethane, propane and butane under anaerobic conditions. Moreover, our study proves nitrate as an additional electron sink for ethane and butane in anaerobic environments, and for the first time demonstrates the use of the fumarate addition pathway in anaerobic ethane oxidation. These findings significantly contribute to our understanding of microbial metabolism of SCGAs in anaerobic environments.
A deep learning phenotyping method for genetic analysis of 3D micro-CT data
Authors: Karshenas A. , Linderoth T. , Zatha R. , Rusuwa B. , Durbin R.
Published: August 2023

The number of Genome-Wide Association Studies (GWAS) has been growing rapidly in recent years due to developments in genotyping and sequencing platforms. When applied to quantitative traits, these and other statistical genetics approaches require large amounts of consistently and accurately measured phenotypes. Here, we introduce a computational toolbox based on deep convolutional neural networks that we have developed to phenotype quantitative traits describing morphology from micro-CT-scan image datasets. We illustrate the use of this Deep Learning Phenotyper (DLP) on a sample set of craniofacial CT scans of 118 samples from two very closely related species of Lake Malawi cichlid fish,Maylandia zebroidesandCynotilapia zebroides. We show that the pipeline constructed and implemented here is capable of measuring morphological skeletal phenotypes with high accuracy. We also demonstrate how this pipeline can be integrated with existing GWAS frameworks to identify candidate association loci. We believe the methods we present here will be valuable for groups studying quantitative morphological traits not only in fishes, but in other vertebrates using CT scan datasets.
Mucosal antibody responses to SARS-CoV-2 booster vaccination and breakthrough infection
Authors: Bhavsar Disha , Singh Gagandeep , Sano Kaori , Gleason Charles , Srivastava Komal ,   PARIS Study Group, Carreño Juan Manuel , Simon Viviana , Krammer Florian
Published: August 2023

Coronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not.

Importance

Antibodies on mucosal surfaces of the upper respiratory tract have been shown to be important for protection from infection with SARS-CoV-2. Here we investigate the induction of serum IgG, saliva IgG and saliva sIgA after COVID-19 mRNA booster vaccination or breakthrough infections.
txtools: an R package facilitating analysis of RNA modifications, structures, and interactions
Authors: Garcia-Campos Miguel Angel , Schwartz Schraga
Published: August 2023

Abstract

We present txtools, an R package that enables the processing, analysis, and visualization of RNA-seq data at the nucleotide-level resolution, seamlessly integrating alignments to the genome with transcriptomic representation. txtools’ main inputs are BAM files and a transcriptome annotation, and the main output is a table, capturing mismatches, deletions, and the number of reads beginning and ending at each nucleotide in the transcriptomic space. txtools further facilitates downstream visualization and analyses. We showcase, using examples from the epitranscriptomic field, how a few calls to txtools functions can yield insightful and ready-to-publish results. txtools is of broad utility also in the context of structural mapping and RNA:protein interaction mapping. By providing a simple and intuitive framework, we believe that txtools will be a useful and convenient tool and pave the path for future discovery. txtools is available for installation from its GitHub repository athttps://github.com/AngelCampos/txtools.
RADAR-IoT: An open-source, interoperable and extensible IoT gateway framework for healthcare and beyond
Authors: Ranjan Yatharth , Chang Jiangeng , Sankesara Heet , Conde Pauline , Rashid Zulqarnain , Sun Shaoxiong , Dobson Richard , Folarin Amos
Published: August 2023

IoT sensors offer a wide range of sensing capabilities, many of which have the potential for health or medical applications. Existing solutions for IoT in healthcare have notable limitations, such as limited I/O protocols, limited cloud platform support, and limited extensibility. Therefore, the development of an open-source Internet of Medical Things (IoMT) gateway solution that addresses these limitations and provides reliability, broad applicability, and utility would be highly desirable. Combining a wide range of sensor data streams from IoT devices with ambulatory mHealth data would open the potential for providing a detailed 360-degree view of the relationship between patient physiology, behaviour, and environment. To harness this potential, RADAR-IoT has been developed as an open-source IoT gateway framework. Its purpose is to connect multiple IoT devices at the edge, perform on-device data analysis, and integrate with cloud-based mobile health platforms such as RADAR-base, enabling real-time data processing.
Patients’ preference and time to finish injection for GnRH agonist and GnRH antagonist in Japanese prostate cancer patients
Authors: Kawahara Takashi , Uemura Hiroji
Published: August 2023

Huggins et al. introduced surgical castration for prostate cancer treatment in 1941. Currently, androgen deprivation therapy (ADT) is key in treating advanced prostate cancer, especially in elderly patients. With the development of gonadotropin-releasing hormone (GnRH) medications, ADT transitioned from surgical to medical castration. From 1985 onwards, various GnRH agonists like Leuprorelin and Goserelin acetate have been used as ADT for prostate cancer. By 2012, a GnRH antagonist, degarelix, was introduced in Japan.

A study at Yokohama City University Medical Center analyzed 851 hormonal injections between August 2018 and February 2019. It assessed the duration from prescription to injection completion and the perceived physical and mental load on patients. Results showed degarelix injections took significantly longer than other treatments. Leuprorelin 22.5mg reduced hospital stays the most, largely due to its 6-month duration and kit formulation. The lengthy process for degarelix, which requires drug dilution and cooling at the injection site due to potential skin reactions, increases its administration time.

Concerning patient burden, leuprorelin 22.5mg ranked the lowest, with little variance from the oral form. A limitation of this study is the administration method of leuprorelin in Japan, which differs from other countries. In summary, the 6-month leuprorelin 22.5mg regimen minimizes hospital time, while degarelix tends to cause the most discomfort for patients.
The Iberian Roma genetic variant server; population structure, susceptibility to disease and adaptive traits
Authors: Mavillard Fabiola , Pérez-Florido Javier , Ortuño Francisco M , Valladares Amador , Álvarez-Villegas Miren L , Roldán Gema , Carmona Rosario , Soriano Manuel , Susarte Santiago , Fuentes Pilar , López-López Daniel , Nuñez-Negrillo Ana María , Carvajal Alejandra , Morgado Yolanda , Arteaga Daniel , Ufano Rosa , Mir Pablo , Gamella Juan F , Dopazo Joaquín , Paradas Carmen , Cabrera-Serrano Macarena
Published: August 2023

The Roma are the most numerous ethnic minority in Europe. The Iberian Roma arrived in the Iberian Peninsula five centuries ago and still today, they keep a strong group identity. Demographic and cultural reasons lie behind a high rate of Mendelian disease often related to founder variants. We have analysed exome data from 119 Iberian Roma individuals collected from 2018 to 2020. A database of variant frequency has been implemented (IRPVS) and made available online. We have analysed the carrier rate of founder private alleles as well as pathogenic variants present in the general population. Significant enrichment in structural variants involving gene clusters related to keratinization and epidermal growth suggest that evolutive mechanisms have developed towards climate and environmental adaptation. IRPVS can be accessed athttp://irpvs.clinbioinfosspa.es/

AUTHOR SUMMARY

Reference data is necessary for the correct interpretation of genetic studies. Although most genetic variants are present in all populations, ancestry has an important impact in the genetic background. For that reason databases of genetic variant in populations are developed specifically for different ethnicities, being an important tool for genetic diagnosis. The Roma are the most numerous ethnic minority in Europe. In this study we have collected samples from healthy Roma individuals from Iberian descent and implemented a database of genetic variant to facilitate genetic diagnosis in this population. Analysis of structural variants that are specific to the Iberian Roma not found in other healthy population for which genetic data are available suggest evolution towards environmental adaptation.
A systematic review evaluating the effectiveness of virtual reality-based well-being interventions for stress reduction in young adults
Authors: Xu Joy , Khanotia Areej , Juni Shmuel , Ku Josephine , Sami Hana , Lin Vallen , Walterson Roberta , Payne Evelyn , Jo Helen , Rahimpoor-Marnani Parmin
Published: August 2023

Background

Adolescents can be especially vulnerable to various stressors as they are still in their formative years and transitioning into adulthood. Hence, it is important for them to have effective stress management strategies. This systematic review investigates current well-being interventions that are aimed at reducing stress among young adults. In particular, interventions using the medium of virtual reality are explored.

Methods

This mixed-methods systematic review follows the PRISMA-P guidelines and articles were gathered for the databases PsycInfo, PubMed, Science Direct, Web of Science, Open Grey and Edutopia. Predetermined criteria and specific keywords were used to search for the articles. Search results were screened and extracted by two independent authors. Any disagreements after reconciliation were settled by a third author. The quality and risk of bias of included studies were assessed using the GRADE Quality Assessment Tool for Quantitative Studies. Studies were analyzed qualitatively.

Results

Among the appraised studies, the effectiveness of virtual reality-based interventions was measured in three contexts: nature, stress, and academics.

Conclusion

Studies using virtual reality interventions, overall, promoted a reduction in stress and an increase in well-being. The findings suggest VR may serve as an accessible and affordable medium of stress reduction for students and young adults. Larger sample sizes, and a greater number of included studies, may be required in future directions.
Microscopic and metatranscriptomic analyses revealed unique cross-domain symbiosis betweenCandidatusPatescibacteria/candidate phyla radiation (CPR) and methanogenic archaea in anaerobic ecosystems
Authors: Kuroda Kyohei , Nakajima Meri , Nakai Ryosuke , Hirakata Yuga , Kagemasa Shuka , Kubota Kengo , Noguchi Taro Q.P. , Yamamoto Kyosuke , Satoh Hisashi , Nobu Masaru K. , Narihiro Takashi
Published: August 2023

To verify the parasitic lifestyle ofCandidatusPatescibacteria in the enrichment cultures derived from a methanogenic bioreactor, we applied multifaceted approaches combining cultivation, microscopy, metatranscriptomic, and protein structure prediction analyses. Cultivation experiments with the addition of exogenous methanogenic archaea with acetate, amino acids, and nucleoside monophosphates and 16S rRNA gene sequencing confirmed the increase in the relative abundance ofCa. Patescibacteria and methanogens. The predominantCa. Patescibacteria wereCa. Yanofskybacteria and 32-520 lineages (to which belongs to classCa. Paceibacteria) and positive linear relationships (r2≥ 0.70) between the relative abundance ofCa. Yanofskybacteria andMethanothrix, suggesting that the tendency of the growth rate is similar to that of the host. By fluorescencein situhybridization (FISH) observations, the FISH signals ofMethanothrixandMethanospirillumcells withCa. Yanofskybacteria and with 32-520 lineages, respectively, were significantly lower than those of the methanogens withoutCa. Patescibacteria, suggesting their parasitic interaction. The TEM and SEM observations also support parasitism in that the cell walls and plugs of these methanogens associated with submicron cells were often deformed. In particular, someMethanothrix-like filamentous cells were dented where the submicron cells were attached. Metatranscriptomic and protein structure prediction analyses identified highly expressed secreted genes from the genomes ofCa. Yanofskybacteria and 32-520, and these genes contain adhesion-related domains to the host cells. Considering the results through the combination of microscopic observations, gene expression, and computational protein modeling, we propose that the interactions betweenCa. Yanofskybacteria and 32-520 belonging to classCa. Paceibacteria and methanogenic archaea are parasitism.
Sputum-spotted solid matrix designed to release diagnostic-gradeMycobacterium tuberculosisDNA demonstrate optimal biocontainment property
Authors: Goyani Krishna H. , Mukhopadhyaya Pratap N.
Published: August 2023

Biosafety quotient of a reagent-coated cellulose matrix designed to releaseMycobacterium tuberculosis(Mtb) DNA from sputum deposited onto it, was determined. Thirty-seven sputum samples infected withMtband 5 sputum samples from healthy individuals were processed and spotted onto the TBSend cards. LiveMtbbacilli were attempted for rescue from the spotted TBSend cards by washing them in phosphate buffer under mild shaking conditions. No liveMtbbacilli could be detected by the BACTEC™ MGIT 960™ TB System from bothMtbinfected as well as non-infected, sample-spotted TBSend cards when they were washed at two different time-points,viz., 1 minute and 15 hours from the time of spotting of the cards with sputum mixed with the preprocessing “spotting” buffer. The study reiterated published finding that chaotropic agents, which is an active component of the TBSend card module, have cent per cent bactericidal properties with regard toMtb.
Anaerobic fungi in the tortoise alimentary tract illuminate early stages of host-fungal symbiosis andNeocallimastigomycotaevolution
Authors: Pratt Carrie J. , Meili Casey H. , Jones Adrienne L. , Jackson Darian K. , England Emma E. , Wang Yan , Hartson Steve , Rogers Janet , Elshahed Mostafa S. , Youssef Noha H.
Published: August 2023

The anaerobic gut fungi (AGF,Neocallimastigomycota) reside in the alimentary tract of herbivores. While their presence in mammals is well documented, evidence for their occurrence in non-mammalian hosts is currently sparse. Here we report on AGF communities in tortoises (familyTestudinidae). Culture-independent surveys of tortoise fecal samples identified a unique AGF community, with three novel deep-branching genera representing >90% of sequences in most samples. Representatives of all genera were successfully isolated under strict anaerobic conditions at 30°C or 39°C. Transcriptomics-enabled phylogenomic and molecular dating analysis indicated an ancient, deep-branching position in the AGF tree for these genera, with an evolutionary divergence time estimate of 104-112 million years ago (Mya). Such estimates push the establishment of animal-Neocallimastigomycotasymbiosis from the early Paleogene (67 Mya) to the early Cretaceous (112 Mya). Further, compared to their mammalian counterparts, tortoise-associated isolates exhibited a more limited capacity for plant polysaccharides metabolism and lacked genes encoding several carbohydrate active enzyme (CAZyme) families mediating their degradation. Finally, we demonstrate that the observed curtailed degradation capacities and reduced CAZyme repretoire in tortoise-associated AGF is driven by the paucity of horizontal gene transfer (HGT) in tortoise-associated AGF genomes, compared to the massive HGT occurrence in mammalian AGF taxa. The reduced CAZyome and overall secretory machinery observed is also reflected in an altered cellulosomal production capacity in tortoise-associated AGF. Our findings provide novel insights into the scope of phylogenetic diversity, ecological distribution, evolutionary history, evolution of fungal-host nutritional symbiosis, and dynamics of genes and traits acquisition inNeocallimastigomycota.

Significance

Anaerobic gut fungi (AGF) are encountered in the rumen and hindgut of mammalian herbivores. However, their occurrence outside their canonical mammalian hosts is currently unclear. We report the identification, isolation, and characterization of novel, deep-branching AGF genera from tortoises. Such discovery expands the phylogenetic diversity and host range of the AGF and revises estimates of the phylum’s evolutionary time to the early Cretaceous (112 Mya). We also demonstrate that tortoise-sourced AGF lack multiple metabolic features compared to their mammalian counterparts, and identify the relative paucity of HGT events in tortoise-associated genera as a major factor underpinning such differences. Our results alter our understanding of the scope of phylogenetic diversity, ecological distribution, and evolutionary history of the AGF.
Bank capital, earnings smoothing and provisioning practices in Nigeria: IFRS and risk evidence
Authors: Salami Abdulai Agbaje , Uthman Ahmad Bukola
Published: August 2023

Purpose

This study empirically tests the use of loan loss provisions (LLPs) for earnings and capital smoothing when emphasis is laid on banks' riskiness and adoption of the International Financial Reporting Standards (IFRSs) in Nigeria.

Design/methodology/approach

Annual bank-level data are hand-extracted between 2007 and 2017 from annual reports of a sample 16 deposit money banks (DMBs), and analysed using appropriate panel regression models subsequent to a number of diagnostic tests including heteroscedasticity, autocorrelation and cross-sectional dependence. The use of both reported LLPs (TLLP) and discretionary LLPs (DLLP) for earnings and capital management is tested to advance the practice in the literature.

Findings

Generally, the study finds that Nigerian DMBs manage capital via LLPs, while mixed results are obtained for earnings smoothing. However, during IFRS, Nigerian DMBs' management of capital is identifiable with TLLP, while smoothing of earnings is peculiar to DLLP. Additionally, evidence of the improvement in loan loss reporting quality expected during IFRS for riskier Nigerian DMBs, could not be attained. This is corroborated by the study's findings of the use of both TLLP and DLLP for earnings and capital management during IFRS by DMBs in solvency crisis against the only use of TLLP to manage capital found for the entire period.

Practical implications

The evidential capital and earnings lopsidedness may subject Nigerian DMBs' going-concern to a lot of questions.

Originality/value

The study sets a foremost record in the empirical test of managerial opportunistic behaviour embedded in earnings and capital concurrently while accounting for loan losses by all categories of Nigerian DMBs in terms of riskiness, following accounting regime change.