bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophage-DB: A comprehensive database to explore diversity, distribution, and ecology of prophages
Authors: Dieppa-Colón Etan , Martin Cody , Anantharaman Karthik
Published: July 2024

Background

Viruses that infect prokaryotes (phages) constitute the most abundant group of biological agents, playing pivotal roles in microbial systems. They are known to impact microbial community dynamics, microbial ecology, and evolution. Efforts to document the diversity, host range, infection dynamics, and effects of bacteriophage infection on host cell metabolism are extremely underexplored. Phages are classified as virulent or temperate based on their life cycles. Temperate phages adopt the lysogenic mode of infection, where the genome integrates into the host cell genome forming a prophage. Prophages enable viral genome replication without host cell lysis, and often contribute novel and beneficial traits to the host genome. Current phage research predominantly focuses on lytic phages, leaving a significant gap in knowledge regarding prophages, including their biology, diversity, and ecological roles.

Results

Here we develop and describe Prophage-DB, a database of prophages, their proteins, and associated metadata that will serve as a resource for viral genomics and microbial ecology. To create the database, we identified and characterized prophages from genomes in three of the largest publicly available databases. We applied several state-of-the-art tools in our pipeline to annotate these viruses, cluster and taxonomically classify them, and detect their respective auxiliary metabolic genes. In total, we identify and characterize over 350,000 prophages and 35,000 auxiliary metabolic genes. Our prophage database is highly representative based on statistical results and contains prophages from a diverse set of archaeal and bacterial hosts which show a wide environmental distribution.

Conclusion

Prophages are particularly overlooked in viral ecology and merit increased attention due to their vital implications for microbiomes and their hosts. Here, we created Prophage-DB to advance our comprehension of prophages in microbiomes through a comprehensive characterization of prophages in publicly available genomes. We propose that Prophage-DB will serve as a valuable resource for advancing phage research, offering insights into viral taxonomy, host relationships, auxiliary metabolic genes, and environmental distribution.
Hemogenic endothelium of the vitelline and umbilical arteries is the major contributor to mouse fetal lympho-myelopoiesis
Authors: Barone Cristiana , Quattrini Giulia , Orsenigo Roberto , Timóteo-Ferreira Filipa , Muratore Alessandro , Cazzola Anna , Patelli Arianna , Soares-da-Silva Francisca , Nicholls Matthew , Mauri Mario , Bombelli Silvia , De Marco Sofia , D’Aliberti Deborah , Spinelli Silvia , Bonalume Veronica , Domingues Alison , Sala Gianluca , Colonna Arianna , D’Errico Elisabetta , D’Orlando Cristina , Bianchi Cristina , Perego Roberto A. , Meneveri Raffaella , De Bruijn Marella F.T.R. , Cumano Ana , Fantin Alessandro , Brunelli Silvia , Piazza Rocco , Azzoni Emanuele
Published: July 2024

Embryonic hematopoiesis consists of distinct waves originating in rapid succession from different anatomical locations. Hematopoietic progenitors appearing earlier than definitive hematopoietic stem cells (HSCs) play key roles in fetal and postnatal life. However, their precise origin, identity and the extent of their contribution need further clarification. To this aim, we took advantage of a genetic fate-mapping strategy in mice that allows labeling and tracking of distinct subsets of hemogenic endothelium (HE). Time-course labeling of hematopoietic progenitors emerging from HE between E8.5 and E9.5, before intra-embryonic definitive HSC generation, revealed a major fetal lympho-myeloid contribution which declined in the adult. Lineage tracing coupled with whole-mount imaging and single-cell RNA sequencing located its source within hematopoietic clusters of vitelline and umbilical arteries. Functional assays confirmed the transient nature of these progenitors. We therefore unveiled a hitherto unidentified early wave of fetal-restricted hematopoietic stem/progenitor cells poised for differentiation that provide a major contribution to pre-natal hematopoiesis.
Coordinated network of T cells and antigen presenting cells regulate tolerance to food
Authors: Rudnitsky Anna , Oh Hanna , Talmor Joanathan , Kedmi Ranit
Published: July 2024

To efficiently absorb nutrients and facilitate microbial commensalism, the host establishes tolerogenic immune programs against dietary and commensal antigens, promoted by peripheral regulatory T cells (pTregs)1,2. Previous research into which antigen-presenting cells (APCs) initiate dietary pTreg responses focused on type 1 DCs (cDC1)3. However, we now report that food-specific pTreg cells are exclusively induced by the recently identified RORγt+ APCs4–8, and not by cDC1. Instead, pTregs interact with cDC1 to regulate the response of food-specific CD8αβ T cells that accumulate in the lamina propria (LP) and epithelial layer of the small intestine (SI) and express memory markers. Upon infection with pathogens that mimic dietary antigens, food-specific CD8αβ cells activate an effector program to potentially guard against ‘Trojan horse’ attacks. Uniquely, after the infection resolves, these cells do not respond to their corresponding dietary antigens, allowing for safe food consumption. Based on our findings, we propose that in response to dietary antigens, dedicated antigen-presenting cells direct a unique CD8αβ response that is coupled to the pTreg program to facilitate protective acute effector responses within the overall strategy of tolerance.
How do brain regions specialised for concrete and abstract concepts align with functional brain networks? A neuroimaging meta-analysis
Authors: Hoffman Paul , Bair Matthew
Published: July 2024

Identifying the brain regions that process concrete and abstract concepts is key to understanding the neural architecture of thought, memory and language. We review current theories of concreteness effects and test their neural predictions in a meta-analysis of 72 neuroimaging studies (1400 participants). Our analysis includes more than twice as many studies as previous meta-analyses, allowing for a more sensitive mapping of these effects across the brain. We also conducted a quantitative assessment of the degree to which concreteness effects aligned with a range of large-scale functional brain networks. Our results suggest that concrete and abstract concepts vary both in the information-processing modalities they engage and in the demands they place on cognitive control processes. Abstract concepts preferentially activated networks for social cognition (particularly for sentences), language and semantic control (particularly when presented as single words). Concrete concepts preferentially activated action processing regions when presented in sentences, though we found no evidence that they activated visual networks. Specialisation for both concept types was present in different parts of the default mode network (DMN), with effects dissociating along a social-spatial axis. Concrete concepts generated greater activation in a medial temporal DMN component, implicated in constructing mental models of spatial contexts and scenes. In contrast, abstract concepts showed greater activation in frontotemporal DMN regions involved in social and language processing. These results align with prior claims that generating models of situations and events is a core DMN function and indicate specialisation within DMN for different aspects of these models.
Gradient Oriented Active Learning for Candidate Drug Design
Authors: Medabalimi Venkatesh
Published: July 2024

One of the primary challenges of drug design is that the complexity of Biology often comes to the fore only when proposed candidates are eventually tested in reality. This necessitates making the discovery process more efficient by making itactively seek what it wants to know of reality. We propose Gradient Oriented Active Learning (GOAL), a technique for optimizing sequence design through active exploration of sequence space that interleaves performing experiments and learning models that propose experiments for the next iteration through gradient based descent in the sequence space. We demonstrate the promise of this method using the challenge of mRNA design as our guiding example. Using computational methods as a surrogate for experimental data, we provide evidence that for certain objectives, if one were restricted by the bandwidth or the number of experiments they can perform in parallel, increasing the number of iterations can still facilitate optimization using very few experiments in total. We show that availability of high-throughput experiments can considerably bring down the number of iterations required. We further investigate the intricacies of performing multi-objective optimization using GOAL.
Performance of three diagnostic tests for tuberculosis among Human Immunodeficiency Virus (HIV) patients presenting to a health facility in an informal urban settlement in Nairobi, Kenya
Authors: Ochola Eunita A. , Mweu Marshal M.
Published: July 2024

The absence of an accurate reference test complicates the evaluation of tuberculosis (TB) diagnostic tests among people living with Human Immunodeficiency Virus (PLWHIV). The objective of this study was to estimate (using Bayesian latent class models [BLCM]) the sensitivity (Se), specificity (Sp) and negative and positive predictive values (NPV and PPV) of sputum smear microscopy (SSM), Xpert Ultra and lipoarabinomannan antigen (LAM) tests for TB among PLWHIV in Nairobi, Kenya.

This cross-sectional study enrolled a total of 190 patients aged ≥ 18 years with presumptive TB seeking treatment at the Kibra Community Health Center Comprehensive Care Centre (CCC) clinic between September 2022 and March 2023. The diagnostic data obtained from the three tests were analysed using a BLCM framework to derive accuracy estimates of the three diagnostic tests.

The Xpert Ultra assay registered a higher Se (85.0; 95% PCI [41.4 – 99.4]) compared to LAM (26.8; 95% PCI [4.7 – 67.6]) and SSM (56.7 [16.4 – 97.4]). However, SSM had the highest Sp (99.6; 95% PCI [97.7 – 100.0]). The Xpert Ultra assay yielded the highest overall combination of Se and Sp at 80.8% (95% PCI [37.0 – 96.5]). On predictive values, SSM recorded the highest PPV at 84.5% (95% PCI [38.4 – 99.4]). Nonetheless, all the tests exhibited noticeably high NPVs (>96%).

An optimal testing approach in this low-prevalence TB setting could entail an initial screening with the more sensitive Xpert Ultra test, with any resultant positives retested with the more specific SSM test - a two-test serial testing strategy.
Investigating the effects of transcutaneous Vagus Nerve Stimulation on motor cortex excitability and inhibition through paired-pulse Transcranial Magnetic Stimulation
Authors: Sara Boscarol , Letizia Turchi , Viola Oldrati , Cosimo Urgesi , Alessandra Finisguerra
Published: July 2024

Transcutaneous Vagus Nerve stimulation (tVNS) has been proposed as a prospective treatment for clinical conditions with altered GABAergic transmission. While possible effects of tVNS on behavioral performance in inhibitory control tasks have been previously reported, neurophysiological evidence showing its effects on GABA-mediated inhibition in the motor cortex is limited. Concurrently, the possible influence of participant’s gender and state conditions remains unexplored. Here, we applied, single- and paired-pulse TMS to the right or the left primary motor in two different groups of participants. We measured corticospinal excitability (CSE), short and long intracortical inhibition (SICI and LICI), cortical silent period (cSP) and intracortical facilitation (ICF) indexes. The measures were taken, in separated sessions of a within-subject design, at baseline prior to tVNS and after delivering active and sham tVNS in the Cymba conchae of the left ear. To exploit state dependent effects and assess the role of tVNS in motor learning, tVNS was applied, during the execution of a computerized visuomotor task. In the left TMS group, we observed better visuomotor performance during active than sham tVNS, regardless of participant’s gender. Interestingly, in both groups, we found a specific increase of SICI, which is mediated by GABAa activity, after active compared to sham-tVNS and baseline evaluations, which was specifically limited to female participants. No effects on CSE, ICF or GABAb-mediated intracortical inhibition indexes were observed. The results show specific effects of tVNS on motor learning and GABAa-mediated motor inhibition, providing supportive evidence for the application of tVNS as an alternative and coadjuvant treatment for disorders featured by altered inhibition mechanisms.
TCMNP: a data processing and visualization database and R package for traditional Chinese medicine network pharmacology
Authors: Liu Jinkun , Feng Jing , Wu Bin , Ying Min
Published: July 2024

Background

Network pharmacology is pivotal for the study of the mechanism of action of traditional Chinese medicine (TCM). However, there are currently some challenges in data processing and visualization for traditional Chinese medicine network pharmacology (TCMNP). We develop the R-environment-based software database and package TCMNP.

Methods

TCMNP is designed for the analysis and visualization of compositions in TCM compounds, herbs, ingredients, corresponding targets and pathway enrichment. Data analysis and visualization in R using “dplyr”, “clusterProfiler”, “ggplot2”, and “circlize” packages, as well as functions of our own making.

Results

TCMNP is designed for the analysis and visualization of compositions in TCM compounds, herbs, ingredients, corresponding targets and pathway. The TCMNP database contains 571 kinds of TCM herbs, 17,118 ingredients, 10,013 diseases, and 15,956 targets. TCMNP simplifies the data analysis process and realizes a complete set of process operations from Chinese herbal compound composition, component and target automatic screening, enrichment analysis visualization, protein interaction and TF and target gene screening. Its built-in functions of various types provide a tidy interface for the visualization of TCM network pharmacology. TCMNP database is freely available athttps://tcmlab.top/tcmr. TCMNP package is freely available athttps://github.com/tcmlab/TCMNP.

Conclusion

The TCMNP database and package provide a comprehensive overview of the interconnections between components of a TCM compound and its potential effects on disease treatment. TCMNP database is available for free athttps://tcmlab.top/tcmr/. TCMNP package is available for free athttps://github.com/tcmlab/TCMNP. We anticipate that TCMNP will help to explore the mechanism of TCM to treat diseases.
Neuron loss in the brain starts in childhood, increases exponentially with age and is halted by GM-CSF treatment in Alzheimer’s disease
Authors: Sillau Stefan H. , Coughlan Christina , Ahmed Md. Mahiuddin , Nair Kavita , Araya Paula , Galbraith Matthew D. , Bettcher Brianne M. , Espinosa Joaquin M. , Chial Heidi J. , Epperson Neill , Boyd Timothy D. , Potter Huntington
Published: July 2024

Aging increases the risk of neurodegeneration, cognitive decline, and Alzheimer’s disease (AD). Currently no means exist to measure neuronal cell death during life or to prevent it. Here we show that cross-sectional measures of human plasma proteins released from dying/damaged neurons (ubiquitin C-terminal hydrolase-L1/UCH-L1 and neurofilament light/NfL) become exponentially higher from age 2-85; UCH-L1 rises faster in females. Glial fibrillary acidic protein (GFAP) concentrations, indicating astrogliosis/inflammation, increase exponentially after age 40. Treatment with human granulocyte-macrophage colony-stimulating factor (GM-CSF/sargramostim) halted neuronal cell death, as evidenced by reduced plasma UCH-L1 concentrations, in AD participants to levels equivalent to those of five-year-old healthy controls. The ability of GM-CSF treatment to reduce neuronal apoptosis was confirmed in a rat model of AD. These findings suggest that the exponential increase in neurodegeneration with age, accelerated by neuroinflammation, may underlie the contribution of aging to cognitive decline and AD and can be halted by GM-CSF/sargramostim treatment.
Laboratory evolution of the bacterial genome structure through insertion sequence activation
Authors: Kanai Yuki , Shibai Atsushi , Yokoi Naomi , Tsuru Saburo , Furusawa Chikara
Published: July 2024

The genome structure critically impacts bacterial physiology, ecology, and evolution. However, its evolution, driven by transposons called insertion sequences (IS), has been challenging to track in laboratories due to its slow pace. Here, we accelerated this process by introducing multiple copies of a high-activity IS intoEscherichia coli. Mimicking bursts of IS copies in host-restricted endosymbionts and pathogens, we evolved the bacteria under relaxed neutral conditions. Within ten weeks, we observed a median of 24.5 IS insertions per genome, comparable to a decade of wild-type evolution. Long-read sequencing revealed extensive IS-mediated genome rearrangements, resulting in novel IS variants and genome size changes exceeding ±5 %. By achieving such drastic genome evolution under relaxed selection, our study establishes a baseline for assessing the fitness effects of IS insertions, genome size changes, and rearrangements. This work paves the way for experimentally studying bacterial genome structure evolution, complementing analyses of genome structures in nature.
Molecular Landscape of Modality-Specific Exercise Adaptation in Human Skeletal Muscle through Large-Scale Multi-OMICs Integration
Authors: Jacques Macsue , Landen Shanie , Sharples Adam P , Garnham Andrew , Schittenhelm Ralf , Stele Joel , Heikkinen Aino , Sillanpää Elina , Ollikainen Miina , Broatch James , Zarekookandeh Navabeh , Hanson Ola , Ekström Ola , Asplund Olof , Lamon Séverine , Alexander Sarah E. , Smith Cassandra , Bauer Carlie , Woessner Mary N. , Levinger Itamar , Teschendorff Andrew E , Gillberg Linn , Blom Ida , Wulff Helge Jørn , Harvey Nicholas R , Haupt Larisa M , Griffiths Lyn R , Deshmukh Atul S. , Pietiläinen Kirsi H , Piirilä Päivi , Seaborne Robert AE , Jones-Freeman Bernadette , Eynon Nir
Published: July 2024

We conducted a large-scale, statistically powered, meta-analysis of exercise adaptations in human skeletal muscles, integrating epigenetic, transcriptomic, transcription factors, and proteomic data across 12 independent cohorts comprising over 1000 participants and 2340 human muscle samples. Our study identified distinctive signatures associated with maximal oxygen consumption (VO2max), and identified five genes robustly intersecting multi-OMIC layers. Notably, transcription factors predominantly functioned as activators across these layers, regulating expression of target genes irrespective of whether DNA methylation levels were low or high, indicating a synergistic effect between TFs and the methylome. Analysis of distinct exercise modalities (aerobic and resistance exercise) revealed unique gene pathways, contrasting with patterns observed in inactivity (muscle disuse) studies. These findings offer a comprehensive understanding of exercise and modality-specific adaptations, shedding light on muscle health and the molecular mechanisms associated with cardiorespiratory fitness, aging, and disease prevention.
Mutational and evolutionary dynamics of non-structural and spike proteins from variants of concern (VOC) of SARS-CoV-2 in India
Authors: Chaudhuri Ankur , Das Subhrangshu , Chakrabarti Saikat
Published: July 2024

Monitoring the genetic diversity and emerging mutations of SARS-CoV-2 still remains to be crucial in India. This study extensively analyzes the lineage dynamics, mutation screening, structural analysis, and phylodynamics of SARS-CoV-2 variants of concern (VOC) in India from October 2020 to September 2023. Predominant variants identified include alpha, beta, delta, and omicron, with delta and omicron making up 76.05% of sequenced genomes. The B.1.617.2 lineage of delta was the major contributor to COVID-19 cases before the rapid rise of omicron. Mutation screening of non-structural proteins (NSPs) and spike revealed distinct profiles for each VOC. Co-mutation patterns/networks of the most frequently observed mutations specific for each VOC were also identified and subsequently structural and energetic alteration of the co-mutants were analyzed using rigorous molecular dynamics simulations. Furthermore, comparative analysis of phylogenetic trees based on genomic and mutational data revealed that nsp1, nsp3, nsp4, nsp13, and nsp14 exhibit strongest association with the increased mutation load across the genome of SARS-CoV-2 in Indian population. Our comparative phylogenetic study also revealed that mutability patterns of nsp14 and spike have highest similarity supporting critical role of nsp14 for SARS-CoV-2 infectivity and persistence. This research provides a comprehensive overview of SARS-CoV-2 evolution in India.
Retinal pigment epithelial cells reduce vascular leak and proliferation in retinal neovessels
Authors: Tzaridis Simone , Aguilar Edith , Dorrell Michael I , Friedlander Martin , Eade Kevin T
Published: July 2024

Retinal pigment epithelial (RPE)-cells possess numerous functions and may respond to stress and damage of the neuroretina. In different neurodegenerative diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, and macular telangiectasia type 2 (MacTel), RPE-cells have been shown to proliferate and migrate into the neuroretina, forming intraretinal pigment plaques. Though pigmentary changes are associated with disease progression, it is not known if their presence is protective or detrimental. In this study, we evaluated the impact of pigment plaques on vascular changes and disease progression in patients with macular telangiectasia type 2 (MacTel), an example of a progressive neurodegenerative retinal disease. We then studied underlying pathomechanisms using a mouse model mirroring these changes, the very-low-density lipoprotein receptor mutant (Vldlr–/–) mouse.

In a retrospective, longitudinal study, we analyzed multimodal retinal images of patients with MacTel and showed that pigment plaques were associated with a decrease in vascular leakage and stabilized neovascular growth. Using genetic approaches, we analyzed changes in expression levels of relevant genes in the RPE and retinas of Vldlr-/- mice during RPE-proliferation and migration. Our data indicated that RPE-cells transitioned from an epithelial to a mesenchymal state (“epithelial-mesenchymal transition”, EMT), proliferated and accumulated along neovessels. Using dextran angiography and immunofluorescence, we demonstrated that the perivascular accumulation of RPE-cells reduced vascular leakage. Pharmacologic inhibition of EMT led to a decrease in pigment coverage and exacerbation of neovascular growth and exudation.

Our findings indicate that the proliferation, migration and perivascular accumulation of RPE-cells may stabilize vascular proliferation and exudation, thereby exerting a protective effect on the diseased retina. We conclude that interfering with this “natural repair mechanism” may have detrimental effects on the course of the disease and should thus be avoided.
Post-Mortemvalidation ofin vivo18kDa Translocator Protein (TSPO) PET as a microglial biomarker
Authors: Wijesinghe Sasvi S. , Rowe James B. , Mason Hannah D. , Allinson Kieren S. J. , Thomas Reuben , Vontobel Davi , Fryer Tim D. , Hong Young T. , Bacioglu Mehtap , Spillantini Maria Grazia , Van den Ameele Jelle , O’Brien John T. , Kaalund Sanne , Malpetti Maura , Quaegebeur Annelies
Published: July 2024

Neuroinflammation is a feature of many neurodegenerative diseases, and can be quantifiedin vivoby PET imaging with radioligands for the translocator protein (TSPO, e.g. [11C]-PK11195). TSPO radioligand binding correlates with clinical severity and predicts clinical progression. However, the cellular substrate of altered TSPO binding is controversial and requires neuropathological validation.

We used progressive supranuclear palsy (PSP) as a demonstrator condition, to test the hypothesis that [11C]-PK11195 PET reflects microglial changes. We included people with PSP-Richardson’s syndrome who had undergone [11C]-PK11195 PET in life. Inpost-mortembrain tissue from the same participants we characterised cell-type specific TSPO expression with double-immunofluorescence labelling and quantified microgliosis in eight cortical and eleven subcortical regions with CD68 immunohistochemistry.

Double-immunofluorescence labelling for TSPO and cell markers showed TSPO expression in microglia, astrocytes, and endothelial cells. Microglial TSPO expression was higher in donors with PSP compared to controls, which was not the case for astrocytic TSPO expression. There was a significant positive correlation between regional [11C]-PK11195 binding potentialante-mortemand the density ofpost-mortemCD68+ phagocytic microglia, as well as microglial TSPO expression.

We conclude that [11C]-PK11195 bindingin vivois driven by microglia and can be interpreted as a biomarker of microglia-mediated neuroinflammation in tauopathies.
Enhanced Gut Microbiome Capacity for Amino Acid Metabolism is associated with Peanut Oral Immunotherapy Failure
Authors: Özçam Mustafa , Lin Din L. , Gupta Chhedi L. , Li Allison , Wheatley Lisa M. , Baloh Carolyn H. , Sanda Srinath , Jones Stacie M. , Lynch Susan V.
Published: July 2024

Peanut Oral Immunotherapy (POIT) holds promise for remission of peanut allergy, though treatment is protracted and successful in only a subset of patients. Because the gut microbiome is linked to food allergy, we sought to identify fecal microbial predictors of POIT efficacy and to develop mechanistic insights into treatment response. Longitudinal functional analysis of the fecal microbiome of children (n=79) undergoing POIT in a first double-blind, placebo-controlled clinical trial, identified five microbial-derived bile acids enriched in fecal samples prior to POIT initiation that predicted treatment efficacy (AUC 0.71). Failure to induce disease remission was associated with a distinct fecal microbiome with enhanced capacity for bile acid deconjugation, amino acid metabolism, and increased peanut peptide degradationin vitro. Thus, microbiome mechanisms of POIT failure appear to include depletion of immunomodulatory secondary bile and amino acids and the antigenic peanut peptides necessary to promote peanut allergy desensitization and remission.
Genetic surveillance reveals low, sustained malaria transmission with clonal replacement in Sao Tome and Principe
Authors: Chen Ying-An , Ng Peng-Yin , Garcia Daniel , Elliot Aaron , Palmer Brian , Assunção Carvalho Ronalg Mendes Costa d’ , Tseng Lien-Fen , Lee Cheng-Sheng , Tsai Kun-Hsien , Greenhouse Bryan , Chang Hsiao-Han
Published: July 2024

Despite efforts to eliminate malaria in Sao Tome and Principe (STP), cases have recently increased. Understanding residual transmission structure is crucial for developing effective elimination strategies. This study collected surveillance data and generated amplicon sequencing data from 980 samples between 2010 and 2016 to examine the genetic structure of the parasite population. The mean multiplicity of infection (MOI) was 1.3, with 11% polyclonal infections, indicating low transmission intensity. Temporal trends of these genetic metrics did not align with incidence rates, suggesting that changes in genetic metrics may not straightforwardly reflect changes in transmission intensity, particularly in low transmission settings where genetic drift and importation have a substantial impact. While 88% of samples were genetically linked, continuous turnover in genetic clusters and changes in drug-resistance haplotypes were observed. Principal component analysis revealed some STP samples were genetically similar to those from Central and West Africa, indicating possible importation. These findings highlight the need to prioritize several interventions such as targeted interventions against transmission hotspots, reactive case detection, and strategies to reduce the introduction of new parasites into this island nation as it approaches elimination. This study also serves as a case study for implementing genetic surveillance in a low transmission setting.
The Relationship between Noise Pollution and Depression and Implications for Healthy Ageing: A Spatial Analysis using Routinely Collected Primary Care Data
Authors: Tsimpida Dialechti , Tsakiridi Anastasia
Published: July 2024

Environmental noise is a significant public health concern, ranking among the top environmental risks to citizens’ health and quality of life. Despite various studies exploring the effects of atmospheric pollution on mental health, spatial investigations into the effects of noise pollution have been notably absent. This study addresses this gap by investigating the association between noise pollution (from road and rail networks) and depression for the first time in England and first explores localised patterns based on area deprivation. Depression prevalence, defined as the percentage of patients with a recorded depression diagnosis was calculated in small areas within Cheshire and Merseyside ICS using the Quality and Outcomes Framework Indicators dataset for 2019. Strategic noise mapping for rail and road noise (LDEN) was employed to quantify noise pollution, indicating a 24-hour annual average noise level with distinct weightings for evening and night periods. The English Index of Multiple Deprivation (IMD) was utilised to represent neighbourhood deprivation. Geographical Weighted Regression and Generalised Structural Equation Spatial Modelling (GSESM) were applied to estimate relationships between transportation noise, depression prevalence, and IMD at the Lower Super Output Area (LSOA) level. While transportation noise showed a low direct effect on depression levels in Cheshire and Merseyside ICS, it significantly mediated other factors linked to depression prevalence. Notably, GSESM revealed that health deprivation and disability was strongly associated (0.62) with depression through the indirect effect of environmental noise, particularly where transportation noise exceeds 55 dB on a 24-hour basis. Comprehending variations in noise exposure across different areas is paramount. This research not only provides valuable insights for informed decision-making but also lays the groundwork for implementing noise mitigation measures. These measures are aimed at addressing mental health inequalities, enhancing the quality of life for the exposed population and supporting a healthier ageing process in urban environments. The findings also carry crucial implications for public health, specifically in tailoring targeted interventions to mitigate noise-related health risks in areas where noise burdens exceed 55 dB, and residents may experience health deprivation and disability.
SpinFlowSim: a blood flow simulation framework for histology-informed diffusion MRI microvasculature mapping in cancer
Authors: Voronova Anna , Grigoriou Athanasios , Bernatowicz Kinga , Simonetti Sara , Serna Garazi , Roson Núria , Escobar Manuel , Vieito Maria , Nuciforo Paolo , Toledo Rodrigo , Garralda Elena , Sala-Llonch Roser , Fieremans Els , Novikov Dmitry S. , Palombo Marco , Perez-Lopez Raquel , Grussu Francesco
Published: July 2024

Diffusion Magnetic Resonance Imaging (dMRI) sensitises the MRI signal to spin motion. This includes Brownian diffusion, but also flow across intricate networks of capillaries. This effect, the intra-voxel incoherent motion (IVIM), enables microvasculature characterisation with dMRI, through metrics such as the vascular signal fractionfVor Apparent Diffusion Coefficient (ADC)D*. The IVIM metrics, while sensitive to perfusion, are in general protocol-dependent, and their interpretation can change depending on the flow regime spins experience during the dMRI measurements (e.g., diffusive vs ballistic), which is in general not known — facts that hamper their clinical utility. Innovative vascular dMRI models are needed to enable thein vivocalculation of biologically meaningful markers of capillary flow. These could have relevant applications in cancer, for instance assessing responses to anti-angiogenic therapies targeting tumor vessels. This paper tackles this need by introducingSpinFlowSim, an open-source simulator of dMRI signals arising from blood flow within pipe networks. SpinFlowSim, tailored for the laminar flow patterns in capillaries, enables the synthesis of highly-realistic microvascular dMRI signals, given networks reconstructed from histology. We showcase the simulator by generating synthetic signals for 15 networks, reconstructed from liver biopsies, and containing cancerous and non-cancerous tissue. Signals exhibit com-plex, non-mono-exponential behaviours, pointing towards the co-existence of different flow regimes within the same network, and diffusion time dependence. We also demonstrate the potential utility of SpinFlowSim by devising a strategy for microvascular property mapping informed by the synthetic signals, focussing on the quantification of blood velocity distribution moments, and of anapparent network branchingindex. These were estimatedin silicoandin vivo, in healthy volunteers and in 13 cancer patients, scanned at 1.5T. In conclusion, realistic flow simulations, as those enabled by SpinFlowSim, may play a key role in the development of the next-generation of dMRI methods for microvascular mapping, with immediate applications in oncology.
Multiplexed detection of febrile infections using CARMEN
Authors: Kamariza M. , McMahon K. , Kim L. , Welch N.L. , Stenson L. , Allan-Blitz L. , Sanders G. , Eromon P. , Iluoreh A.M. , Sijuwola A. , Ope-ewe O.O. , Ayinla A.O. , l’Anson C. , Baudi I. , Paye M.F. , Wilkason C. , Lemieux J. , Ozonoff A. , Stachler E. , Happi C.T. , Sabeti P.C.
Published: July 2024

Detection and diagnosis of bloodborne pathogens are critical for patients and for preventing outbreaks, yet challenging due to these diseases’ nonspecific initial symptoms. We advanced CRISPR-based Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN) technology for simultaneous detection of pathogens on numerous samples. We developed three specialized panels that target viral hemorrhagic fevers, mosquito-borne viruses, and sexually transmitted infections, collectively identifying 23 pathogens. We used deep learning to design CARMEN assays with enhanced sensitivity and specificity, validating them and evaluating their performance on synthetic targets, spiked healthy normal serum samples, and patient samples forNeisseria gonorrhoeaein the United States and for Lassa and mpox virus in Nigeria. Our results show multiplexed CARMEN assays match or outperform individual assay RT-PCR in sensitivity, with matched specificity. These findings underscore CARMEN’s potential as a highly effective tool for rapid, accurate pathogen detection for clinical diagnosis and public health surveillance.
Heart-retina time analysis using electrocardiogram-coupled time-resolved dynamic optical coherence tomography
Authors: Valmaggia Philippe , Wolleb Julia , Bieder Florentin , Scholl Hendrik P.N. , Cattin Philippe C. , Maloca Peter M.
Published: July 2024

The eye and the heart are two closely interlinked organs, and many diseases affecting the cardiovascular system manifest in the eye. To contribute to the understanding of blood flow propagation towards the retina, we developed a method to acquire electrocardiogram (ECG) coupled time-resolved dynamic optical coherence tomography (OCT) images. This method allows for continuous synchronised monitoring of the cardiac cycle and retinal blood flow dynamics. The dynamic OCT measurements were used to calculate time-resolved blood flow profiles using fringe washout analysis. The relative fringe washout was computed to generate the flow velocity profiles within arterioles at the optic nerve head rim. We found that the blood column between the heart and the retina propagates within one cardiac cycle, denoting the arrival time as the heart-retina time (HRT). In a group of healthy subjects, the HRT was 144 ± 19 ms (mean ± SD). The HRT could provide a novel potential biomarker for cardiovascular health in direct relation to retinal perfusion.
Breathome discriminate Ischemic Heart Disease
Authors: Marzoog Basheer Abdullah , Chomakhidze Peter , Gognieva Daria , Gagarina Nina Vladimirovna , Silantyev Artemiy , Suvorov Alexander , Fominykha Ekaterina , Kopylov Philipp
Published: July 2024

Background

Ischemic heart disease (IHD) impacts the quality of life and has the highest mortality rate in between other cardiovascular disease in the globe.

Objectives

IHD early diagnosis, management, and prevention remain underestimated due to the poor diagnostic and therapeutic strategies including the early prevention methods.

Aims

To assess the changes in the exhaled breath analysis, volatile organic compounds (VOCs), in patients with ischemic heart disease confirmed by stress computed tomography myocardial perfusion (CTP) imaging.

Materials and methods

A single center observational study included 80 participants from Moscow. The participants aged ≥ 40 years and given a written consent to participate in the study. Both groups, G1=31 with vs G2=49 without post stress induced myocardial perfusion defect, passed cardiologist consultation, anthropometric measurements, blood pressure and pulse rate, echocardiography, real time breathing at rest into PTR-TOF-MS-1000, cardio-ankle vascular index, performing bicycle ergometry, and immediately after performing bicycle ergometry repeating the breathing analysis into the PTR-TOF-MS-1000, and after three minutes from the second breath, repeat the breath into the PTR-TOF-MS-1000, then performing CTP. LASSO regression with nested cross-validation was used to find association between VOCs and existence of perfusion defect. Statistical processing was carried out using the R programming language v4.2 and Python v.3.10 [^R], STATISTICA, and IBM SPSS.

Results

The specificity 77.6 % [95 % confidence interval (CI); 0.666; 0.889], sensitivity 83.9 % [95 % CI; 0.692; 0.964], and accuracy of the diagnostic method using exhaled breath analysis, area under the curve (AUC) 83.8 % [95 % CI; 0.73655857; 0.91493173]. Whereas, the AUC of the bicycle ergometry 50.7 % [95 % CI; 0.388; 0.625], specificity 53.1 % [95 % CI; 0.392; 0.673], and sensitivity 48.4 % [95 % CI; 0.306; 0.657].

Conclusion

VOCs analysis appear to discriminate individuals with and without IHD with clinically acceptable diagnostic accuracy.

Other

The exhaled breath analysis reflects the myocardiocytes metabolomic signature and related intercellular homeostasis changes and regulation perturbances. Exhaled breath analysis poses a promise result to improve the diagnostic accuracy of the physical stress tests.
The novel duodenal isolateStreptococcus salivariusAGIRA0003 promotes barrier dysfunction and IgG responses in functional dyspepsia
Authors: Burns Grace L. , Wark Jasmine A. , Hoedt Emily C. , Minahan Kyra , Sherwin Simonne , Bruce Jessica K. , Lim Yenkai , Teh Jing Jie , Jamaluddin M. Fairuz B. , Soh Wai Sinn , Caban Shandelle , Fowler Sophie , Almazi Juhura G. , Woldu Ameha S. , Dun Matthew D. , Tanwar Pradeep S. , Potter Michael D. E. , Shanahan Erin R. , Holtmann Gerald , Morrison Mark , Talley Nicholas J. , Keely Simon
Published: July 2024

Background and aims

Functional dyspepsia (FD) is a highly prevalent disorder of gut-brain interaction (DGBI) that is associated with an altered duodenal microbiota, unexplained low grade duodenal inflammation and altered intestinal permeability. This study aimed to investigate if novel FD-derived bacterial isolates elicited immune responses in FD and the capacity of an immune-stimulating isolate, AGIRA0003 to breach the duodenal epithelial barrier.

Methods

Bacterial lysates were investigated for immune reactivity using immunoblotting of patient plasma. Immunoblots were probed with plasma from FD patients (n=44, 46.6±17.5 years, 79.6% female) or controls (n=30, 48.9±15.7 years, 63.3% female). Peripheral gut-homing T cells were quantified by flow cytometry and histological analysis used to investigate duodenal biopsies. Polarised Caco-2 cells and FD duodenal spheroids (n=4 lines) were exposed toStreptococcus salivariusAGIRA0003 at a multiplicity of infection of 10 bacterial cells to 1 mammalian cell for 6 hours.

Results

The presence of plasma IgG antibodies againstS. salivariusAGIRA0003 was significantly associated with FD (χ215.7, 1,p<0.0001). Patients with these IgG antibodies had increased gut-homing lymphocytes (0.33±0.77% vs 1.00±1.46%,p=0.046). Strain AGIRA0003, but not related commensal strains, disrupted tight junction proteins in Caco-2 monolayers, and decreased claudin 1 (CLDN1; 0.49±0.11,p=0.03), desmocollin 2 (DSC2; 0.64±0.33,p=0.03) and desmoglein 2 (DSG2; 0.30±0.12,p=0.03) in spheroid monolayers. In addition, DSC2 (2.19±0.97 vs 1.48±0.85,p=0.02) and DSG2 (23.22±15.92 vs 12.38±7.34,p=0.04) protein levels were decreased in IgG+FD biopsies compared to controls.

Conclusions

S. salivariusAGIRA0003 is a potential pathobiont capable of impairing duodenal epithelial barrier defences that elicits an immune response in FD patients.
Prospective classification of functional dependence: Insights from machine learning and the Canadian Longitudinal Study on Aging
Authors: van Allen Zachary M. , Boisgontier Matthieu P.
Published: July 2024

Purpose

Functional dependence is a multifactorial health condition affecting well-being and life expectancy. To better understand the mechanisms underlying this condition, we aimed to identify the variables that best prospectively classify adults with and without limitations in basic and instrumental activities of daily living.

Methods

A filtering approach was used to select the best predictors of functional status from 4,248 candidate predictors collected in 39,927 participants aged 44 to 88 years old at baseline. Several machine learning models using the selected baseline variables (2010-2015) were compared for their ability to classify participants by functional status (dependent vs. independent) at follow up (2018-2021) on a training dataset (n=31,941) of participants from the Canadian Longitudinal Study on Aging. The best performing model was then examined on a test dataset (n=7,986) to confirm sensitivity, specificity, and accuracy.

Results

Eighteen candidate baseline variables were identified as the best predictors of functional status at follow up. Logistic regression was the best performing model for classifying participants by functional status and achieved balanced accuracy of 81.9% on the test dataset. The absence of functional limitations at baseline, stronger grip strength, being free of pain and of chronic conditions, being a female, having a drivers license, and good memory were associated with greater odds functionally independence at follow-up. In contrast, older age, psychological distress, walking slowly, being retired, having one or more chronic conditions, and never going for walks were associated with greater odds of functional dependence at follow-up.

Conclusion

Functional status can be best prospectively estimated by health condition, age, muscle strength, short-term memory, physical activity, psychological distress, and sex. These predictors can estimate functional status over 6 years ahead with high accuracy. This early identification of people at risk of functional dependence allows sufficient time for the implementation of interventions aiming to delay functional decline.
Hypnotherapy for major depressive disorder: a systematic review of randomized clinical trials
Authors: Souza Filipe Luís , Moura Murilo Schiefler , Elkins Gary , Silva Juliana Vieira Almeida
Published: July 2024

Introduction:Major Depressive Disorder (MDD) is one of the most debilitating diseases worldwide and has seen a significant increase in diagnoses during the pandemic, demanding more and better therapeutic tools to manage the post-pandemic scenario.Objective:The aim of this systematic review is to provide a comprehensive analysis of the last 20 years of clinical research on Hypnotherapy (HT) to determine whether this intervention has evidence to support its recommendation for the treatment of MDD.Methods:This review included only randomized clinical trials (RCTs) involving adult populations diagnosed with MDD, regardless of the severity level (mild, moderate, or severe) according to any validated diagnostic criteria, compared to a control group (active treatment or none), with any follow-up duration and free access to the manuscript. The bibliographic survey was planned to be as sensitive as possible, conducted across seven distinct databases: MEDLINE (PubMed), Embase, CENTRAL, PsycINFO, Scopus, ScieELO, and Latin American and Caribbean Health Sciences Literature (LILACS). To identify potentially eligible studies in the grey literature, researchers also searched the U.S. National Library of Medicine (ClinicalTrials.gov). The risk of bias was assessed by two independent investigators using Cochrane’s revised tool (RoB 2), and the final judgment was made by consensus. To better analyze the included studies, the certainty of the evidence was evaluated through the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Due to the lack of comparable studies, it was not possible to perform a meta-analysis; therefore, the studies were graphically displayed in Descriptive Forest Plots.Results:There is very low-quality evidence suggesting that hypnosis-based interventions may reduce the severity of depression, which precludes the clinical recommendation of this intervention for patients in the real world, pending the production of better evidence of effectiveness and safety, although no evidence of significant adverse effects was found.Other:This review was pre-registered with PROSPERO and can be accessed using the registration number CRD42023409631.
Correlation analysis of latent hepatitis B virus infection gene mutation in unpaid blood donors
Authors: Yu Wei , Wang Fang , Liu Qiang
Published: July 2024

Objective

To analyze the HBV S region gene mutation in serum samples of occult hepatitis B virus (HBV) infection (OB1), and to further analyze the mechanism of gene mutation and OBI.

Methods

Blood samples from unpaid blood donors from January 2022 to December 2023 were collected and analyzed for serology, liver function indicators, viral load and gene mutation.

Results

A total of 90 OBI cases were detected, the detection rate was 0.051%, and the incidence of OBI was correlated with age. The sequence amplification of s region in the blood samples showed the presence of C type and B type genes, both of which occurred in the hydrophilic region.

Conclusion

There is no abnormal liver function between OBI and hepatitis B population, and there is no difference in viral load between different serum modes. Mutations in the HBVS region are more likely to cause OBI, which provides a scientific basis for more sensitive HBV detection.