bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroaffective profiles are associated with e-cigarette use
Authors: Versace Francesco , Kypriotakis George 
Published: February 2022

AbstractIntroductionIdentifying the psychophysiological underpinnings of cue-induced compulsive nicotine use will provide new targets for relapse prevention treatments. We tested whether neuroaffective responses to motivationally relevant stimuli are associated with cue-induced nicotine self-administration. We hypothesized that smokers with stronger neuroaffective responses to nicotine-related cues than to pleasant stimuli (C>P) are more vulnerable to cue-induced nicotine self-administration than smokers with stronger neuroaffective responses to pleasant stimuli than to nicotine-related cues (P>C).MethodsSmokers (N=36) looked at pleasant, unpleasant, neutral, and nicotine-related images signaling that an electronic nicotine delivery system (ENDS) was immediately available for use. We measured event-related potentials (a direct measure of cortical activity) and computed the amplitude of the late positive potential, a robust index of motivational salience. We used k-means cluster analysis to identify individuals characterized by the C>P or the P>C neuroaffective profile. We compared the ENDS use frequency in the two groups using quantile regression for counts.ResultsCluster analysis assigned 18 smokers to the C>P profile and 18 smokers to the P>C profile. Smokers with the C>P neuroaffective profile used the ENDS significantly more often than smokers with the P>C profile. Significant differences in the number of puffs persisted across different quantiles.ConclusionsThese results support the hypothesis that individual differences in the tendency to attribute motivational salience to drug-related cues underlie vulnerability to cue-induced drug self-administration.ImplicationsBy linking brain reactivity profiles to nicotine self-administration, we identified a neuroaffective biomarker that could guide the development of personalized treatments to prevent smoking relapse.
A Nile Grass Rat Transcriptomic Landscape Across 22 Organs By Ultra-deep Sequencing and Comparative RNA-seq pipeline (CRSP)
Authors: Toh Huishi , Bagheri Atefeh , Dewey Colin , Stewart Ron , Yan Lili , Clegg Dennis , Thomson James A. , Jiang Peng 
Published: February 2022

AbstractRNA sequencing (RNA-seq) has been a widely used high-throughput method to characterize transcriptomic dynamics spatiotemporally. However, typical RNA-seq data analysis pipelines depend on either a sequenced genome or corresponding reference transcripts or them both. This restriction makes the use of RNA-seq for species lacking both of sequenced genomes and corresponding reference transcripts challenging. Nile grass rat (Arvicanthis niloticus) is a diurnal rodent species with several unique characteristics making it as a useful model to study diet-induced type 2 diabetes and other physiological or behavioral processes due to its diurnal nature. However, there is neither a high-quality annotated Nile grass rat genome nor a reference transcript sets available so far, making it technically challenging to perform large-scale RNA-seq based transcriptomic studies. Although we are working on the first draft of Nile grass rat genome, a well annotated genome typically requires several rounds of manually reviewing curated transcripts and can take years to achieve. To solve this problem, we developed a Comparative RNA-Seq Pipeline (CRSP), integrating a comparative species strategy but not depending on a specific sequenced genome or species-matched reference transcripts. Benchmarking suggests the CRSP tool can achieve high accuracy to quantify gene expression levels. In this study, we generated the first ultra-deep (2.3 billion × 2 paired-end) Nile grass rat RNA-seq data from 59 biopsy samples representing 22 major organs, providing a unique resource and spatial gene expression reference for using Nile grass rat as a model to study human diseases. To facilitate a general use of CRSP, we also characterized the number of RNA-seq reads required for accurate estimation via simulation studies. CRSP and documents are available at: https://github.com/pjiang1105/CRSP.HighlightsCRSP is a novel software tool which can quantify gene expression levels from RNA-seq data for species lacking both a sequenced genome and corresponding reference transcripts.Nile grass rat is a unique diurnal rodent species (day active but not night active) with several unique characteristics making it as a useful model to study diet-induced type 2 diabetes and other physiological or behavioral processes due to its diurnal nature.We generated the first ultra-deep (2.3 billion × 2 paired-end reads) Nile grass rat RNA-seq data from 59 biopsy samples representing 22 major organs, providing a unique resource and spatial transcriptomic reference (e.g., tissue gene expression baseline) for using Nile grass rat as a model to study human diseases.
Spatial and temporal epidemiology of SARS-CoV-2 virus lineages in Teesside, UK, in 2020: effects of socio-economic deprivation, weather, and lockdown on lineage dynamics
Authors: Moss E.D. , Rushton S.P. , Baker P. , Bashton M. , Crown M.R. , dos Santos R.N. , Nelson A. , O’Brien S.J. , Richards Z. , Sanderson R.A. , Yew W.C. , Young G.R. , McCann C.M. , Smith D.L. 
Published: February 2022

AbstractBackgroundSARS-CoV-2 emerged in the UK in January 2020. The UK government introduced control measures including national ‘lockdowns’ and local ‘tiers’ in England to control virus transmission. As the outbreak continued, new variants were detected through two national monitoring programmes that conducted genomic sequencing. This study aimed to determine the effects of weather, demographic features, and national and local COVID-19 restrictions on positive PCR tests at a sub-regional scale.MethodsWe examined the spatial and temporal patterns of COVID-19 in the Teesside sub-region of the UK, from January to December 2020, capturing the first two waves of the epidemic. We used a combination of disease mapping and mixed-effect modelling to analyse the total positive tests, and those of the eight most common virus lineages, in response to potential infection risk factors: socio-economic deprivation, population size, temperature, rainfall, government interventions, and a government restaurant subsidy (“Eat Out to Help Out”).ResultsTotal positive tests of SARS-CoV-2 were decreased by temperature and the first national lockdown (the only one to include school closures), while deprivation, population, the second national lockdown, and the local tiered interventions were associated with increased cases. The restaurant subsidy and rainfall had no apparent effect. The relationships between positive tests and covariates varied greatly between lineages, likely due to the strong heterogeneity in their spatial and temporal distributions. Cases during the second wave appeared to be higher in areas that recorded fewer first-wave cases, however, an additional model showed the number of first-wave cases was not predictive of second-wave cases.DiscussionNational and local government interventions appeared to be ineffective at the sub-regional level if they did not include school closures. Examination of viral lineages at the sub-regional scale was less useful in terms of investigating covariate associations but may be more useful for tracking spread within communities. Our study highlights the importance of understanding the effects of government interventions in local and regional contexts, and the importance of applying local restrictions appropriately within such settings.
TNF signaling is required for castration-induced vascular damage preceding prostate cancer regression
Authors: Krolewski John J. , Singh Shalini , Sha Kai , Agrawal Neha Jaiswal , Turowski Steven G. , Pan Chunliu , Rich Laurie J. , Seshadri Mukund , Nastiuk Kent L. 
Published: February 2022

AbstractThe mainstay treatment for locally advanced, recurrent, or metastatic prostate cancer (PrCa) is androgen deprivation therapy (ADT). ADT causes prostate cancers to shrink in volume, or regress, by inducing epithelial tumor cell apoptosis. In normal, non-neoplastic murine prostate, androgen deprivation via castration induces prostate gland regression that is dependent on TNF signaling. Besides this direct mechanism of action, castration has also been implicated in an indirect mechanism of prostate epithelial cell death which has been described as vascular regression. The initiating event is endothelial cell apoptosis and/or increased vascular permeability. This subsequently leads to reduced blood flow and perfusion, and then hypoxia, which may enhance epithelial cell apoptosis. Castration-induced vascular regression has been observed in both normal and neoplastic prostate. We used photoacoustic, power Doppler, and contrast-enhanced ultrasound imaging, and CD31 immunohistochemical staining of the microvasculature to assess vascular integrity in the period immediately following castration, enabling us to test the role of TNF signaling in vascular regression. In two mouse models of androgen-responsive prostate cancer, TNF signaling blockade using a soluble TNFR2 ligand trap reversed the functional aspects of vascular regression as well as structural changes in the microvasculature, including reduced vessel wall thickness, cross-sectional area and vessel perimeter length. These results demonstrate that TNF signaling is required for vascular regression, most likely inducing endothelial cell apoptosis and increasing vessel permeability. Since TNF is also the critical death receptor ligand for prostate epithelial cells, we propose that TNF is a multi-purpose, comprehensive signal within the prostate cancer micro-environment mediating prostate cancer regression following androgen deprivation.SIGNIFICANCEThese studies define TNF as the mediator of androgen deprivation therapy-induced functional and structural vascular damage in prostate tumors.
A wearable platform for closed-loop stimulation and recording of single-neuron and local field potential activity in freely-moving humans
Authors: Topalovic Uros , Barclay Sam , Ling Chenkai , Alzuhair Ahmed , Yu Wenhao , Hokhikyan Vahagn , Chandrakumar Hariprasad , Rozgic Dejan , Jiang Wenlong , Basir-Kazeruni Sina , Maoz Sabrina L. , Inman Cory S. , Gill Jay , Bari Ausaf , Fallah Aria , Eliashiv Dawn , Pouratian Nader , Fried Itzhak , Suthana Nanthia , Markovic Dejan 
Published: February 2022

AbstractAdvances in technologies that can record and stimulate deep-brain activity in humans have led to impactful discoveries within the field of neuroscience and contributed to the development of novel therapies for neurological and psychiatric disorders. Further progress, however, has been hindered by device limitations in that recording of single-neuron activity during freely-moving behaviors in humans has not been possible. Additionally, implantable neurostimulation devices, currently approved for human use, have limited stimulation programmability and lack full-duplex bi-directional capability. Here, we developed a wearable bi-directional closed-loop neuromodulation system (Neuro-stack) and used it to record single-neuron and local field potential activity during stationary and ambulatory behavior in humans. Together with a highly flexible and customizable stimulation capability, the Neuro-stack provides an opportunity to investigate the neurophysiological basis of disease, develop improved responsive neuromodulation therapies, explore brain function during naturalistic behaviors in humans, and consequently, bridge decades of neuroscientific findings across species.
Belayer: Modeling discrete and continuous spatial variation in gene expression from spatially resolved transcriptomics
Authors: Ma Cong , Chitra Uthsav , Zhang Shirley , Raphael Benjamin J. 
Published: February 2022

AbstractSpatially resolved transcriptomics (SRT) technologies measure gene expression at known locations in a tissue slice, enabling the identification of spatially varying genes or cell types. Current approaches for these tasks assume either that gene expression varies continuously across a tissue or that a slice contains a small number of regions with distinct cellular composition. We propose a model for SRT data that includes both continuous and discrete spatial variation in expression, and an algorithm, Belayer, to estimate the parameters of this model from layered tissues. Belayer models gene expression as a piecewise linear function of the relative depth of a tissue layer with possible discontinuities at layer boundaries. We use conformal maps to model relative depth and derive a dynamic programming algorithm to infer layer boundaries and gene expression functions. Belayer accurately identifies tissue layers and infers biologically meaningful spatially varying genes in SRT data from brain and skin tissue samples.
Heterologous SARS-CoV-2 IgA neutralising antibody responses in convalescent plasma
Authors: Davis Samantha K , Selva Kevin John , Lopez Ester , Haycroft Ebene R , Lee Wen Shi , Wheatley Adam K , Juno Jennifer A , Adair Amy , Pymm Phillip , Redmond Samuel J , Gherardin Nicholas A , Godfrey Dale I , Tham Wai-Hong , Kent Stephen J , Chung Amy W 
Published: February 2022

AbstractFollowing infection with SARS-CoV-2, virus-specific antibodies are generated which can both neutralise virions and clear infection via Fc effector functions. The importance of IgG antibodies for protection and control of SARS-CoV-2 has been extensively reported. In comparison, other antibody isotypes including IgA have been poorly characterized. Here we characterized plasma IgA from 41 early convalescent COVID-19 subjects for neutralisation and Fc effector functions. We find that convalescent plasma IgA from >60% of the cohort have the capacity to inhibit the interaction between wild-type RBD and ACE2. Furthermore, a third of the cohort induced stronger IgA-mediated inhibition of RBD binding to ACE2 than IgG, when tested at equivalent concentrations. Plasma IgA and IgG from the cohort, broadly recognize similar RBD epitopes and showed similar ability to inhibit ACE2 from binding 22 of 23 different prevalent RBD proteins with single amino acid mutations. Plasma IgA was largely incapable of mediating antibody-dependent phagocytosis in comparison to plasma IgG. Overall, convalescent plasma IgA contributes to neutralisation towards wild-type RBD and various RBD single mutants in most subjects, although this response is heterogeneous and less potent than IgG.
An AI-assisted Tool For Efficient Prostate Cancer Diagnosis
Authors: Oner Mustafa Umit , Ng Mei Ying , Giron Danilo Medina , Xi Cecilia Ee Chen , Xiang Louis Ang Yuan , Singh Malay , Yu Weimiao , Sung Wing-Kin , Wong Chin Fong , Lee Hwee Kuan 
Published: February 2022

AbstractPathologists diagnose prostate cancer by core needle biopsy. For low-grade and low-volume cases, the pathologists look for the few malignant glands out of hundreds within a core. They may miss the few malignant glands, resulting in repeat biopsies or missed therapeutic opportunities. This study developed a multi-resolution deep learning pipeline detecting malignant glands in core needle biopsies to help pathologists effectively and accurately diagnose prostate cancer in low-grade and low-volume cases. The pipeline consisted of two stages: the gland segmentation model detected the glands within the sections and the multi-resolution model classified each detected gland into benign vs. malignant. Analyzing a gland at multiple resolutions provided the classification model to exploit both morphology information (of nuclei and glands) and neighborhood information (for architectural patterns), important in prostate gland classification. We developed and tested our pipeline on the slides of a local cohort of 99 patients in Singapore. The images were made publicly available, becoming the first digital histopathology dataset of prostatic carcinoma patients of Asian ancestry. Our pipeline successfully classified the core needle biopsy parts (81 parts: 50 benign and 31 malignant) into benign vs. malignant. It achieved an AUROC value of 0.997 (95% CI: 0.987 - 1.000). Moreover, it produced heatmaps highlighting the malignancy of each gland in core needle biopsies. Hence, our pipeline can effectively assist pathologists in core needle biopsy analysis.
Glypican-3 (GPC3) is associated with MCPyV-negative status and impaired outcome in Merkel Cell Carcinoma
Authors: Muralidharan Sujatha , Kervarrec Thibault , Weiss Glen J. , Samimi Mahtab 
Published: February 2022

ABSTRACTBackgroundMerkel cell carcinoma (MCC) is an aggressive skin cancer, related to the Merkel Cell Polyomavirus (MCPyV) in 80% of cases. Immune checkpoint inhibitors provide sustained benefit in about half of MCC patients with advanced disease. Glypican-3 (GPC3) is an oncofetal tumor antigen that is an attractive target for chimeric antigen receptor T cell therapy due to its highly restricted expression on normal tissue and high prevalence in several solid tumors. GPC3 was previously found to be expressed in MCC but its association with tumor characteristics or prognosis has not been reported.ObjectivesTo investigate the expression of GPC3 in MCC by immunohistochemistry (IHC) and its association with tumor characteristics, MCPyV status, and patient outcome.MethodsThe GC33 antibody clone was validated for GPC3 IHC staining of tumor specimens in comparison to an established GPC3 IHC antibody. A tissue microarray of tumors collected from an ongoing cohort of MCC patients was stained for GPC3 by IHC using GC33 antibody. Association of GPC3 positivity with baseline characteristics, MCPyV status (quantitative PCR) and outcome (death from MCC, recurrence) were assessed by Fisher’s exact tests and Cox regression analysis.ResultsAmong 62 tumors from 59 patients, 42 samples (67.7%) were GPC3-positive. GPC3 expression was more frequently observed in females (p=0.048) and MCPyV-negative tumors (p=0.021). In the multivariate analysis, GPC3 expression was associated with increased death from disease (CSS) (hazard ratio [HR] 4.05, 95% CI 1.06-15.43), together with advanced age (HR 4.85, 95% CI 1.39-16.9) and male gender (HR 4.64, 95% CI 1.31-16.41).ConclusionsGPC3 expression is frequently expressed in MCC tumors, especially MCPyV-negative cases, and is associated with increased risk of death. The high prevalence of surface GPC3 makes it a putative drug target.
Stability Criterion for the Assembly of Hybrid Lipid-Polymer-Nucleic Acid Nanoparticles
Authors: Paris Juan L. , Gaspar Ricardo , Coelho Filipe , De Beule Pieter A. A. , Silva Bruno F. B. 
Published: February 2022

AbstractHybrid lipid-polymer-nucleic acid nanoparticles (LPNPs) provide unique delivery strategies for nonviral gene therapy. Since LPNPs consist of multiple components that can undergo different pairwise interactions between them, LPNPs are difficult to prepare and characterize. Here we demonstrate that the interaction between the polycation (polylysine) and DNA is robust through an innovative implementation of fluorescence cross-correlation spectroscopy, implying that the polycation is not displaced by cationic liposomes in the formation process. Hence, the polycation-DNA cores (polyplexes) and liposome shells must be oppositely charged to associate. Furthermore, we prove that the liposome:polyplex number ratio (ρN) is the primary critical parameter to predict stable LPNP formation. We establish thatρN≥ 1 is required to ensure that every polyplex is enveloped by a liposome, avoiding the coexistence of oppositely charged species and thereby inhibiting aggregation. We expect our observations to be valid for the formation of many other LPNPs and composite nanomaterials.
An atlas of gene expression variation across the Caenorhabditis elegans species
Authors: Zhang Gaotian , Roberto Nicole M. , Lee Daehan , Hahnel Steffen R. , Andersen Erik C. 
Published: February 2022

AbstractPhenotypic variation in diverse organism-level traits have been studied in Caenorhabditis elegans wild strains, but differences in gene expression and the underlying variation in regulatory mechanisms are largely unknown. Here, we use natural variation in gene expression to connect genetic variants to differences in organismal- level traits, including drug and toxicant responses. We performed transcriptomic analysis on 207 genetically distinct C. elegans wild strains to study natural regulatory variation of gene expression. Using this massive dataset, we performed genome-wide association mappings to investigate the genetic basis underlying gene expression variation and revealed complex genetic architectures. We found a large collection of hotspots enriched for expression quantitative trait loci across the genome. We further used mediation analysis to understand how gene expression variation could underlie organism-level phenotypic variation for a variety of complex traits. These results reveal the natural diversity in gene expression and possible regulatory mechanisms in this keystone model organism, highlighting the promise of gene expression variation in shaping phenotypic diversity.
A “step too far” or “perfect sense”? A qualitative study of British adults’ views on mandating COVID-19 vaccination and vaccine passports
Authors: Stead Martine , Ford Allison , Eadie Douglas , Biggs Hannah , Elliott Claire , Ussher Michael , Bedford Helen , Angus Kathryn , Hunt Kate , MacKintosh Anne Marie , Jessop Curtis , MacGregor Andy 
Published: February 2022

AbstractBackgroundDebate is ongoing about mandating COVID-19 vaccination to maximise uptake. Policymakers must consider whether to mandate, for how long, and in which contexts, taking into account not only legal and ethical questions but also public opinion. Implementing mandates among populations who oppose them could be counterproductive.MethodsQualitative telephone interviews (Feb-May 2021) with British adults explored views on vaccine passports and mandatory vaccination. Participants (n=50) were purposively selected from respondents to a probability-based national survey of attitudes to COVID-19 vaccination, to include those expressing vaccine-hesitancy. Data were analysed thematically.FindingsSix themes were identified in participants’ narratives concerning mandates: (i) mandates are a necessary and proportionate response for some occupations to protect the vulnerable and facilitate the resumption of free movement; (ii) mandates undermine autonomy and choice; (iii) mandates represent an over-reach of state power; (iv) mandates could potentially create ‘vaccine apartheid’; (v) the importance of context and framing; and (vi) mandates present considerable feasibility challenges. Those refusing vaccination tended to argue strongly against mandates. However, those in favour of vaccination also expressed concerns about freedom of choice, state coercion and social divisiveness.DiscussionTo our knowledge, this is the first in-depth UK study of public views on COVID-19 vaccine mandates. It does not assess support for different mandates but explores emotions, principles and reasoning underpinning views. Our data suggest that debate around mandates can arouse strong concerns and could entrench scepticism. Policymakers should proceed with caution. While surveys can provide snapshots of opinion on mandates, views are complex and further consultation is needed regarding specific scenarios.