bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in children aged 6 months to 5 years
Authors: Aglipay Mary , Maguire Jonathon , Swayze Sarah , Tuite Ashleigh , Mamdani Muhammad , Keown-Stoneman Charles , Birken Catherine , Kwong Jeffrey C 
Published: June 2023

ABSTRACTImportanceData on mRNA-1273 (Moderna) vaccine effectiveness in children aged 6 months to 5 years are limited.ObjectiveTo assess mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization among children aged 6 months to 5 years.Design, Setting, and ParticipantsA test-negative study using linked health administrative data in Ontario, Canada. Participants included symptomatic children aged 6 months to 5 years who were tested by RT-PCR.ExposuresmRNA-1273 vaccination.Main Outcomes and MeasuresSymptomatic SARS-CoV-2 infection and COVID-19-related hospitalization.ResultsWe included 3467 test-negative controls and 572 test-positive cases. Receipt of mRNA-1273 was associated with reduced symptomatic SARS-CoV-2 infection (VE=90%; 95%CI: 53, 99%) and COVID-19-related hospitalization (VE=82%; 95%CI: 4, 99%) ≥7 days after the second dose.Conclusions and RelevanceOur findings suggest mRNA-1273 vaccine effectiveness is initially strong against symptomatic SARS-CoV-2 infection and hospitalization in children aged 6 months to 5 years. Further research is needed to understand long-term effectiveness and the need for booster doses.
How does corruption influence health system efficiency? A case study of two counties in Kenya
Authors: Munywoki Joshua , Nyawira Lizah , Musiega Anita , Njuguna Rebecca G , Tsofa Benjamin , Hanson Kara , Molyneux Sassy , Normand Charles , Jemutai Julie , Barasa Edwine 
Published: June 2023

ABSTRACTObjectiveEfficiency gains are one potential pathway to unlocking additional resources for the health sector. Given that corruption has been cited as a key cause of inefficiency in the health sector, the objective of this study was to examine the influence of corruption on the efficiency of county health systems in Kenya.Design, setting and analysisWe conducted a qualitative case study in two counties in Kenya. We developed a conceptual framework from a literature review to guide the development of tools and analysis. We collected qualitative data through in-depth interviews (n=26) with county, sub-county, and health facility level respondents across the two counties. We analyzed the data collected using a framework approach.ResultsCorrupt practices reported in the case study counties included non-merit-based recruitment and training of health workers, supply of substandard goods, equipment and infrastructure; theft, embezzlement and misuse of public funds and property; and informal payments. These practices were perceived to impact negatively on health system efficiency by leading to a direct loss of health sector resources, increase in operational costs, poor quality of care, reduced staff motivation and productivity, and reduced access to healthcare services.ConclusionThe efficiency of county health systems could be enhanced by implementing anti-corruption strategies to tackle the identified corrupt practices.Strengths and limitations of this studyTo the best of our knowledge, this paper is the first of its kind to focus on how corruption affects attainment of health sector goals in KenyaOur reported findings focus on only two out of forty-seven counties in Kenya.Transferability of our findings ought to be interpreted with consideration to contextual factors that shaped reported corruption practicesWe found study respondents to be cautious when reporting their experiences and perceptions on health sector corruption. It is possible that social desirability bias affected response from our study participantsGiven the sensitivity and difficulty of corruption as a study topic, this study was not able to evaluate the effectiveness of existing anti-corruption strategies in Kenya
The effect of natural terrestrial gamma radiation emissions and environmental radon levels on the incidence of cutaneous squamous cell carcinoma of the head and neck
Authors: Couto-González Ivan , Arenaz-Búa Jorge , Taboda-Suárez Antonio , García-García Abel 
Published: June 2023

AbstractThe effects of ionising radiation on the development of cutaneous squamous cell carcinoma have been previously studied in environments in which the levels of ionising radiation have been increased by artificial sources. The purpose of this study is to determine the role that environmental radon concentration and natural gamma radiation emissions may play in the development of head and neck cutaneous squamous cell carcinoma in a geographical area which is known to have high levels of radon and natural terrestrial gamma radiation emissions. A total of 284 patients diagnosed with cutaneous squamous cell carcinoma during the 26-month observation period were included in the study. The overall incidence was 37.33 cases/100,000 people-year. The mean of environmental radon concentration according to their council of residence was 116.69 Bq/m3(40.05) and the mean of natural terrestrial gamma radiation emitted according to their council of residence was 14.25 μRad/hour (3.86). The multiple linear regression analysis revealed that only mean natural terrestrial gamma radiation emissions in the council of residence (P < 0.05), carrying out an outdoor profession (P < 0.05) and the mean number of hours of sunlight per year in the council of residence (P = 0.03) were found to have statistical significance on the incidence of head and neck cutaneous squamous cell carcinoma. Emissions of natural terrestrial gamma radiation have never been proposed as a factor having an influence on the development of cutaneous neoplasms. The implications that this could have in areas with naturally high terrestrial gamma radiation emissions should be more exhaustively studied to assess the true weight of this factor.
Chronic Overlapping Pain Conditions and Nociplastic Pain
Authors: Johnston Keira J.A. , Signer Rebecca , Huckins Laura M. 
Published: June 2023

AbstractChronic Overlapping Pain Conditions (COPCs) are a subset of chronic pain conditions commonly comorbid with one another and more prevalent in women and assigned female at birth (AFAB) individuals. Pain experience in these conditions may better fit with a new mechanistic pain descriptor, nociplastic pain, and nociplastic type pain may represent a shared underlying factor among COPCs. We applied GenomicSEM common-factor genome wide association study (GWAS) and multivariate transcriptome-wide association (TWAS) analyses to existing GWAS output for six COPCs in order to find genetic variation associated with nociplastic type pain, followed by genetic correlation (linkage-disequilibrium score regression), gene-set and tissue enrichment analyses. We found 24 independent single nucleotide polymorphisms (SNPs), and 127 unique genes significantly associated with nociplastic type pain, and showed nociplastic type pain to be a polygenic trait with significant SNP-heritability. We found significant genetic overlap between multisite chronic pain and nociplastic type pain, and to a smaller extent with rheumatoid arthritis and a neuropathic pain phenotype. Tissue enrichment analyses highlighted cardiac and thyroid tissue, and gene set enrichment analyses emphasized potential shared mechanisms in cognitive, personality, and metabolic traits and nociplastic type pain along with distinct pathology in migraine and headache. We use a well-powered network approach to investigate nociplastic type pain using existing COPC GWAS output, and show nociplastic type pain to be a complex, heritable trait, in addition to contributing to understanding of potential mechanisms in development of nociplastic pain.
Effects of Chronic Pain Diagnoses on the Antidepressant Efficacy of Transcranial Magnetic Stimulation
Authors: Totonchi Afshar H. , Fishbein J. N. , Martinez E. J. , Chu G. M. , Shenasa M. A. , Ramanathan D. , Herbert M. S. 
Published: June 2023

AbstractBackgroundMajor depressive disorder (MDD) and chronic pain are highly comorbid and bidirectionally related, such that MDD typically interferes with chronic pain treatment and vice versa. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) is effective in treating MDD, but additional research is needed to determine if chronic pain interferes with rTMS for MDD.MethodParticipants were 124 veterans (Mage=49.1, SD=13.8) scheduled for 30 sessions of rTMS across six weeks at the Veterans Affairs San Diego Healthcare System. Depression severity was monitored weekly using the Patient Health Questionnaire-9. Having any pain diagnosis, low back pain, or migraine/headache were assessed by chart review. Latent basis models were used to estimate change and change-by-pain diagnosis in depression scores during rTMS treatment.ResultsA total of 92 participants (74%) had a documented pain diagnosis, 58 (47%) had low back pain, and 32 (26%) had migraine/headache. Depression scores initially decreased (linear slope estimate=-2.04, SE=0.26,p<.0001), but the rate of decrease slowed over time (quadratic slope estimate=0.18, SE=0.04,p<.001). Having any pain diagnosis, low back pain, or migraine/headache did not significantly differentiate overall amount of change. However, individuals with headache/migraine showed greater initial improvement but then an even faster slowing in rate of decrease than those without headache/migraine.ConclusionsHaving any pain diagnosis, low back pain, or headache/migraine did not significantly interfere with improvement in depression; however, headache/migraine affected the timing of change. These data contribute to the ongoing support of rTMS as a viable treatment option for comorbid populations.
LSD increases sleep duration the night after microdosing
Authors: Allen Nathan , Jeremiah Aron , Murphy Robin , Sumner Rachael , Forsyth Anna , Hoeh Nicholas , Menkes David B , Evans William , Muthukumaraswamy Suresh , Sundram Frederick , Roop Partha 
Published: June 2023

AbstractMicrodosing psychedelic drugs, at a level below the threshold to induce hallucinations, is an increasingly common lifestyle practise. However, the effects of microdosing on sleep have not been previously reported. Here we report results from a Phase 1 randomised controlled trial in which 80 healthy adult male volunteers received a six week course of either LSD (10 µg) or placebo with doses self-administered every third day. Participants used a commercially available sleep/activity tracker for the duration of the trial. Data from 3231 nights of sleep showed that on the night after microdosing participants in the LSD group slept an extra 24.3 minutes per night (95% Confidence Interval 10.3 - 38.3 minutes) compared to placebo - with no reductions of sleep observed on the dosing day itself. There were no changes in the proportion of time spent in various sleep stages or in participant physical activity. These results show clear modification of the physiological sleep requirements in healthy volunteers who microdose, and may have implications for the proposed therapeutic effects of microdosing in mood disorders such as major depressive disorder where sleep is frequently disturbed. The clear, clinically significant, changes in objective measurements of sleep observed are difficult to explain as a placebo effect.
Application of Deep Learning Models into the Prediction of Interleukin-6 and -8 Cytokines in Sickle Cell Anemia Patients
Authors: Nguyen Dylan , Abraham Lukas , Amatya Ashesh 
Published: June 2023

AbstractInterleukin-6 (IL6) and Interleukin-8 (IL8) are cytokines related to general immune function, but within Sickle Cell Anemia (SCA) patients, their overproduction tends to cause auto-immune reactions. These vital cytokines engage in the pathophysiology of SCA, but the extent to which they are associated with the genetics of the disease requires further exploration. This research paper seeks to further the study of IL6 and IL8 in SCA patients as well as the possibilities to predict their presence in patients based on Haptoglobin alleles and various other hematological factors using artificial neural networks. This was done through a cross-sectional study of 60 sickle anemia patients and 74 healthy individuals who provided the basis for the data of this study. The deep learning model found a non-linear correlation between the Haptoglobin alleles and the production of IL6 and IL8, predicting their over presence in SCA patients with an accuracy of 90.9% and r-squared value of 0.88 based on the given inputs. The machine learning models built in this paper have the potential to accelerate the development of targeted treatments and diagnoses to those suffering from Sickle Cell Anemia and its specific immune complications.
Population encoding of stimulus features along the visual hierarchy
Authors: Dyballa Luciano , Rudzite Andra M. , Hoseini Mahmood S. , Thapa Mishek , Stryker Michael P. , Field Greg D. , Zucker Steven W. 
Published: June 2023

AbstractThe retina and primary visual cortex (V1) both exhibit diverse neural populations sensitive to diverse visual features. Yet it remains unclear how neural populations in each area partition stimulus space to span these features. One possibility is that neural populations are organized into discrete groups of neurons, with each group signaling a particular constellation of features. Alternatively, neurons could be continuously distributed across feature-encoding space. To distinguish these possibilities, we presented a battery of visual stimuli to mouse retina and V1 while measuring neural responses with multi-electrode arrays. Using machine learning approaches, we developed a manifold embedding technique that captures how neural populations partition feature space and how visual responses correlate with physiological and anatomical properties of individual neurons. We show that retinal populations discretely encode features, while V1 populations provide a more continuous representation. Applying the same analysis approach to convolutional neural networks that model visual processing, we demonstrate that they partition features much more similarly to the retina, indicating they are more like big retinas than little brains.
Label-free analysis of bacterial growth and lysis at the single-cell level using droplet microfluidics and object detection-oriented deep learning
Authors: Tiwari Anuj , Nikolic Nela , Anagnostidis Vasileios , Gielen Fabrice 
Published: June 2023

AbstractBacteria identification and counting at the small population scale is important to many applications in the food safety industry, the diagnostics of infectious diseases and the study and discovery of novel antimicrobial compounds. There is still a lack of easy to implement, fast and accurate methods to count populations of motile cells at the single-cell level. Here, we report a label-free method to count and localize bacterial cells freely swimming in microfluidic anchored picolitre droplets. We used the object detection oriented YOLOv4 deep learning framework for cell detection from bright-field images obtained with an automated Z-stack setup. The neural network was trained to recognizeEscherichia colicell morphology with an average precision of approximately 84%. This allowed us to accurately identify individual cell division events, enabling the study of stochastic bacterial growth starting from initial populations as low as one cell. This work also demonstrates the ability to study single cell lysis in the presence of T7 lytic bacterial viruses (phages). The high precision in cell numbers facilitated the visualization of bacteria-phage interactions over timescale of hours, paving the way towards deciphering phage life cycles in confined environments.
Microglia produce the amyloidogenic ABri peptide in familial British dementia
Authors: Arber Charles , Casey Jackie M. , Crawford Samuel , Rambarack Naiomi , Yaman Umran , Wiethoff Sarah , Augustin Emma , Piers Thomas M. , Rostagno Agueda , Ghiso Jorge , Lewis Patrick A. , Revesz Tamas , Hardy John , Pocock Jennifer M. , Houlden Henry , Schott Jonathan M. , Salih Dervis A. , Lashley Tammaryn , Wray Selina 
Published: June 2023

AbstractMutations inITM2Bcause familial British, Danish, Chinese and Korean dementias. In familial British dementia (FBD) a mutation in the stop codon of theITM2Bgene (also known asBRI2) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein to be extended by 11 amino acids. This fragment, termed amyloid-Bri (ABri), is highly insoluble and forms extracellular plaques in the brain. ABri plaques are accompanied by tau pathology, neuronal cell death and progressive dementia, with striking parallels to the aetiology and pathogenesis of Alzheimer’s disease. The molecular mechanisms underpinning FBD are ill-defined. Using patient-derived induced pluripotent stem cells, we show that expression ofITM2B/BRI2is 34-fold higher in microglia than neurons, and 15-fold higher in microglia compared with astrocytes. This cell-specific enrichment is supported by expression data from both mouse and human brain tissue. ITM2B/BRI2 protein levels are higher in iPSC-microglia compared with neurons and astrocytes. Consequently, the ABri peptide was detected in patient iPSC-derived microglial lysates and conditioned media but was undetectable in patient-derived neurons and control microglia. Pathological examination of post-mortem tissue support ABri expression in microglia that are in proximity to pre-amyloid deposits. Finally, gene co-expression analysis supports a role for ITM2B/BRI2 in disease-associated microglial responses. These data demonstrate that microglia are the major contributors to the production of amyloid forming peptides in FBD, potentially acting as instigators of neurodegeneration. Additionally, these data also suggest ITM2B/BRI2 may be part of a microglial response to disease, motivating further investigations of its role in microglial activation. This has implications for our understanding of the role of microglia and the innate immune response in the pathogenesis of FBD and other neurodegenerative dementias including Alzheimer’s disease.
Lymphocytic choriomeningitis arenavirus requires cellular COPI and AP-4 complexes for efficient replication and virion production
Authors: Byford Owen , Shaw Amelia B. , Tse Hiu Nam , Todd Eleanor J. A. A. , Álvarez-Rodríguez Beatriz , Hewson Roger , Fontana Juan , Barr John N. 
Published: June 2023

AbstractLymphocytic choriomeningitis virus (LCMV) is a bisegmented negative-sense RNA virus classified within theArenaviridaefamily of theBunyaviralesorder. LCMV is associated with fatal disease in immunocompromised populations, and as the prototypical arenavirus, acts as a model for the many serious human pathogens within theArenaviridaefamily. Here, we examined the dependence of LCMV multiplication on cellular trafficking components using a recombinant LCMV expressing enhanced green fluorescent protein in conjunction with a curated siRNA library. The screen revealed a requirement for subunits of both the coat protein 1 (COPI) coatamer and adapter protein 4 (AP-4) complexes. By rescuing a recombinant LCMV harbouring a FLAG tagged GP-1 envelope spike (rLCMV-GP1-FLAG) we showed infection resulted in marked co-localization of COPI and AP-4 component with both LCMV nucleoprotein (NP) and GP-1. Time-of-addition studies using brefeldin A (BFA), an ARF-I inhibitor that prevents formation of both COPI and AP-4 complexes, suggested these cellular components were involved in late stages of the LCMV multiplication cycle. Consistent with this finding, BFA treatment at similar late time-points resulted in a marked redistribution of NP and GP-1, and subsequent loss of COPI/AP-4 co-localization. Finally, titration of released virus within supernatant of BFA-treated cells revealed a 10-fold decrease in viral titres, greater than the 2-fold BFA-mediated reduction in NP expression. Taken together, these findings suggest COPI and AP-4 complexes are important host cell factors that are required for efficient LCMV assembly and egress.ImportanceArenaviruses are rodent-borne, segmented, negative-sense RNA viruses, with several members responsible for fatal human disease, with the prototypic member LCMV being under-recognised as a pathogen capable of inflicting neurological infections with fatal outcome. Here, we assessed the impact of siRNA knockdown of host cell trafficking genes on LCMV multiplication. We reveal the requirement of host cellular COPI and AP-4 complexes for efficient LCMV multiplication, acting late in the replication cycle, at the stages of egress and assembly. Collectively, our findings improve the understanding of arenaviruses host-pathogen interactions and reveal novel cellular trafficking pathways required during infection. Moreover, this study may lead to the discovery of novel therapeutic targets for arenaviruses to prevent serious human disease.
Homing in on the rare virosphere reveals the native host of giant viruses
Authors: Fromm Amir , Hevroni Gur , Vincent Flora , Schatz Daniella , Martinez-Gutierrez Carolina A. , Aylward Frank O. , Vardi Assaf 
Published: June 2023

SummaryGiant viruses (phylum Nucleocytoviricota) are globally distributed in aquatic ecosystems1,2. They play major roles as evolutionary drivers of eukaryotic plankton3and regulators of global biogeochemical cycles4. Recent metagenomic studies have significantly expanded the known diversity of marine giant viruses1,5–7, but we still lack fundamental knowledge about their native hosts, thereby hindering our understanding of their lifecycle and ecological importance. Here, we aim to discover the native hosts of giant viruses using a novel, sensitive single-cell metatranscriptomic approach. By applying this approach to natural plankton communities, we unraveled an active viral infection of several giant viruses, from multiple lineages, and identified their native hosts. We identify a rare lineage of giant virus (Imitervirales-07) infecting a minute population of protists (class Katablepharidaceae) and revealed the prevalence of highly expressed viral-encoded cell-fate regulation genes in infected cells. Further examination of this host-virus dynamics in a temporal resolution suggested this giant virus controls its host population demise. Our results demonstrate how single-cell metatranscriptomics is a sensitive approach for pairing viruses with their authentic hosts and studying their ecological significance in a culture-independent manner in the marine environment.
MORPHOGENIC VERSUS MITOGENIC ROLES OF SHH ARE SEGREGATED ON DISTINCT EXOSOMES REGULATED BY CELLULAR RAB7 LEVELS
Authors: Walvekar Ankita , Pandey Shivangi , Kamat Siddhesh S. , Damodar Sharat , Ladher Raj K. , Vyas Neha 
Published: June 2023

AbstractThe secreted signaling molecule, Sonic hedgehog (Shh) is involved in patterning and growth of various embryonic tissues across species. This lipid-anchored protein is secreted on extracellular vesicles to activate signaling. Shh has two functions during spinal cord development, acting as a morphogen to pattern the ventral neural tube and a mitogen to maintain neural progenitors. Here, we find that these activities are segregated on to two distinct pools of exosomes. Shh secreted on a classical exosomal pool (Shh-P150) is able to activate ventral threshold targets in the neural tube. In contrast, the mitogenic activity, is elicited by a lighter exosomal pool (Shh-P450). We further show that cellular environment plays a major role in regulating the biogenesis of P150 versus P450 by modulating Rab7 levels. We find that active Rab7 is necessary for ventral neural tube patterning through the regulation of Shh-P150 secretion. The cellular mechanisms involved in packaging and secretion of Shh with different partners on P150 or P450 pools may be more general, enabling the separation of functional activities of signaling molecules during development and disease.