bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccinating Australia: How long will it take?
Authors: Hanly Mark , Churches Tim , Fitzgerald Oisín , McIntyre C Raina , Jorm Louisa 
Published: February 2021

AbstractThe Australian Government’s COVID-19 vaccine rollout strategy is scheduled to commence in late February 2021 and aims to vaccinate the Australian adult population by the end of October 2021. The task of vaccinating some 20 million people within this timeframe presents considerable logistical challenges. Key to meeting this target is the rate of vaccine delivery: the number of vaccine doses that can be administered per day. In the opening phase, high priority groups will receive the Pfizer/BioNTech vaccine through hospital hubs at an initial rate of 80,000 doses per week. However, pending regulatory approval, the currently announced plan appears to be to distribute the AstraZeneca vaccine to the bulk of the popluation through a combination of general practices and community pharmacies. Here, we run a series of projections to estimate how long it will take to vaccinate the Australian population under different assumptions about the rate of vaccine administration as well as the schedule for second doses and prevalence of vaccine hesitancy. Our analysis highlights the ambitious rate of vaccine administration that will be neccessary to meet the Australian Government completion target of October 2021. A rate of 200,000 doses per day would comfortably meet that target; 80,000 doses a day would see roll-out extended until mid-2022. Speed is of the essence when it comes to vaccine rollout: protecting the population quickly will minimise the risk of sporadic and costly lockdowns lockdowns and the potential for small, local clusters getting out of control and sparking new epidemic waves. The government should gather all its resources to maximise the daily vaccination rate, ideally aiming to ramp up administration to at least 200,000 doses per day as quickly as possible. Quickly achieving and maintaining this pace will likely require dedicated large-scale vaccination sites that are capable of delivering thousands of doses a week in addition to the enthusiastic participation of GP practices and community pharmacies around the country. Lessons on the neccessary logistical planning, including coordination of delivery, ultra-cold-chain storage and staffing, can potentially be learned from Israel, where between 7,000 and 20,000 vaccinations per million population have been delivered daily throughout January.
Rapid vaccination and early reactive partial lockdown will minimize deaths from emerging highly contagious SARS-CoV-2 variants
Authors: Reeves Daniel B , Bracis Chloe , Swan David A. , Moore Mia , Dimitrov Dobromir , Schiffer Joshua T. 
Published: February 2021

AbstractThe goals of SARS-CoV-2 vaccination programs are to maximally reduce cases and deaths, and to limit the amount of time required under lockdown. Using a mathematical model calibrated to data from King County Washington but generalizable across states, we simulated multiple scenarios with different vaccine efficacy profiles, vaccination rates, and case thresholds for triggering and relaxing partial lockdowns. We assumed that a contagious variant is currently present at low levels. In all scenarios, it rapidly becomes dominant by early summer. Low case thresholds for triggering partial lockdowns during current and future waves of infection strongly predict lower total numbers of COVID-19 infections, hospitalizations and deaths in 2021. However, in regions with relatively higher current seroprevalence, there is a predicted delay in onset of a subsequent surge in new variant infections. For all vaccine efficacy profiles, increasing vaccination rate lowers the total number of infections and deaths, as well as the total number of days under partial lockdown. Due to variable current estimates of emerging variant infectiousness, vaccine efficacy against these variants, vaccine refusal, and future adherence to masking and physical distancing, we project considerable uncertainty regarding the timing and intensity of subsequent waves of infection. Nevertheless, under all plausible scenarios, rapid vaccination and early implementation of partial lockdown are the two most critical variables to save the greatest number of lives.
Modelling the Impact of Prevention and Treatment Interventions on HIV and Hepatitis C Virus Transmission Among People Who Inject Drugs in Kenya
Authors: Stone Jack , Fraser Hannah , Walker Josephine G , Mafirakureva Nyashadzaishe , Mundia Bernard , Cleland Charles , Kigen Bartilol , Musyoki Helgar , Waruiru Wanjiru , Ragi Allan , Bhattacharjee Parinita , Chhun Nok , Lizcano John , Akiyama Matthew J , Cherutich Peter , Kurth Ann , Luhmann Niklas , Vickerman Peter 
Published: February 2021

AbstractBackgroundPeople who inject drugs (PWID) in Kenya have a high prevalence of HIV (14-26%) and HCV (11-36%). Needle and syringe programmes (NSP) and antiretroviral therapy (ART) have high coverage among PWID, while HCV treatment and opioid substitution therapy (OST) access is low.MethodsA dynamic model of HIV (sexual and injecting-related) and HCV (injecting-related) transmission among PWID was calibrated using Bayesian methods to data from Nairobi and the Coastal region. We projected the impact of existing coverage levels of interventions (ART: 64-66%; OST: 4-7%; NSP: 54-56%) in each setting, and the impact over 2020-2030 of increasing the coverage of OST (50%) and NSP (75%; ‘full HR’), ART (UNAIDS 90-90-90 target), HCV treatment (1000 over 5 years), and reducing HIV sexual risk by 75%. We estimated HCV treatment levels needed to reduce HCV incidence by 90% with or without full HR.FindingsSince 2013, HR has averted 15.1-20.6% (range in medians across settings) of HIV infections and 29.0-31.6% of HCV infections across Nairobi and the Coastal region, with most impact being due to NSP. Conversely, ART has only averted <5% of HIV infections since 2004 because of sub-optimal viral suppression (28-48%). Going forward, Full HR and ART could reduce HIV incidence by 58.2-62.0% and HCV incidence by 62.6-81.6% by 2030 across these settings. If sexual risk is also reduced, HIV incidence would reduce by 77.1-81.4%. Alongside full HR, treating 896 PWID over 2020-2025 could reduce HCV incidence by 90% by 2030.InterpretationExisting interventions have had moderate impact on HIV and HCV transmission in Kenya, but may have substantial impact if scaled-up. However, to achieve HIV and HCV elimination, reductions in sexual risk are needed and a scale-up in HCV treatment.FundingGlobal Fund, MDM
Cofilin pathology is a new player on α-synuclein-induced spine impairment in models of hippocampal synucleinopathy
Authors: Oliveira da Silva MI , Santejo M , Babcock IW , Magalhães A , Minamide LS , Castillo E , Gerhardt E , Fahlbusch C , Swanson RA , Outeiro TF , Bamburg JR , Liz MA 
Published: February 2021

AbstractCognitive dysfunction and dementia are presently recognized as major complications in α-synucleinopathies, namely in Dementia with Lewy Bodies (DLB) and Parkinson’s disease with dementia (PDD). In these disorders, α-Synuclein (αSyn) accumulation affects severely the hippocampus by inducing synaptic dysfunction which culminates in cognitive impairment. To characterize the mechanisms underlying αSyn-induced neuronal dysfunction we analysed the effect of overexpression or extracellular administration of αSyn on hippocampal neurons. We observed that αSyn induces the dysregulation of the actin-binding protein cofilin and its assembly into rod structures in a mechanism mediated by the cellular prion protein (PrPC). Moreover, we unraveled cofilin pathology as mediator of αSyn-induced dendritic spine impairment in hippocampal neurons. Importantly, in a synucleinopathy mouse model with cognitive impairment we validated cofilin dysregulation and synaptic dysfunction at the same age when cognitive deficits were observed. Our data supports cofilin as a novel player on hippocampal synaptic dysfunction triggered by αSyn on Lewy Body dementias.
Combined influence of food availability and agricultural intensification on a declining aerial insectivore
Authors: Garrett Daniel R. , Pelletier Fanie , Garant Dany , Bélisle Marc 
Published: February 2021

AbstractAerial insectivores show worldwide population declines coinciding with shifts in agricultural practices. Increasing reliance on certain agricultural practices is thought to have led to an overall reduction in insect abundance that negatively affects aerial insectivore fitness. The relationship between prey availability and the fitness of insectivores may thus vary with the extent of agricultural intensity. It is therefore imperative to quantify the strength and direction of these associations. Here we used data from an 11-year study monitoring the breeding of Tree Swallows (Tachycineta bicolor) and the availability of Diptera (their main prey) across a gradient of agricultural intensification in southern Québec, Canada. This gradient was characterized by a shift in agricultural production, whereby landscapes composed of forage and pastures represented less agro-intensive landscapes and those focusing on large-scale arable row crop monocultures, such as corn (Zea mays) or soybean (Glycine max) that are innately associated with significant mechanization and agro-chemical inputs, represented more agro-intensive landscapes. We evaluated the landscape characteristics affecting prey availability, and how this relationship influences the fledging success, duration of the nestling period, fledgling body mass, and wing length as these variables are known to influence the population dynamics of this species. Diptera availability was greatest within predominately forested landscapes, while within landscapes dominated by agriculture, it was marginally greater in less agro-intensive areas. Of the measured fitness and body condition proxies, both fledging success and nestling body mass were positively related to prey availability. The impact of prey availability varied across the agricultural gradient as fledging success improved with increasing prey levels within forage landscapes yet declined in more agro-intensive landscapes. Finally, after accounting for prey availability, fledging success was lowest, nestling periods were the longest, and wing length of fledglings were shortest within more agro-intensive landscapes. Our results highlight the interacting roles that aerial insect availability and agricultural intensification have on the fitness of aerial insectivores, and by extension how food availability may interact with other aspects of breeding habitats to influence the population dynamics of predators.Open ResearchData are not yet provided (option 4) as they are being used for other research projects. We affirm that data will be permanently archived if the paper is accepted for publication on the Dryad repository.
Identification of a Nervous System Gene Expression Signature in Colon Cancer Stem Cells Reveals a Role for Neural Crest RegulatorsEGR2andSOX2in Tumorigenesis
Authors: Regan Joseph L. , Schumacher Dirk , Staudte Stephanie , Steffen Andreas , Lesche Ralf , Toedling Joern , Jourdan Thibaud , Haybaeck Johannes , Golob-Schwarzl Nicole , Mumberg Dominik , Henderson David , Győrffy Balázs , Regenbrecht Christian R.A. , Keilholz Ulrich , Schäfer Reinhold , Lange Martin 
Published: February 2021

SUMMARYRecent data support a hierarchical model of colon cancer driven by a population of cancer stem cells (CSCs). Greater understanding of the mechanisms that regulate CSCs may therefore lead to more effective treatments. Serial limiting dilution xenotransplantation assays of colon cancer patient-derived tumors demonstrated ALDHPositivecells to be enriched for tumorigenic self-renewing CSCs. In order to identify CSC modulators, we performed RNA-sequencing analysis of ALDHPositiveCSCs from a panel of colon cancer patient-derived organoids (PDOs) and xenografts (PDXs). These studies demonstrated CSCs to be enriched for embryonic and neural development gene sets. Functional analyses of genes differentially expressed in both ALDHPositivePDO and PDX CSCs demonstrated the neural crest stem cell (NCSC) regulator and wound response geneEGR2to be required for CSC tumorigenicity and to control expression of homeobox superfamily embryonic master transcriptional regulatorHOXgenes and the embryonic and neural stem cell regulatorSOX2. In addition, we identifyEGR2, HOXA2, HOXA4, HOXA5, HOXA7, HOXB2, HOXB3and the tumor suppressorATOH1as new prognostic biomarkers in colorectal cancer.
Unravelling the Physiological Correlates of Mental Workload Variations in Tracking and Collision Prediction Tasks: Implications for Air Traffic Controllers
Authors: John Alka Rachel , Singh Avinash K , Do Tien-Thong Nguyen , Eidels Ami , Nalivaiko Eugene , Gavgani Alireza Mazloumi , Brown Scott , Bennett Murray , Lal Sara , Simpson Ann M. , Gustin Sylvia M , Double Kay , Walker Frederick Rohan , Kleitman Sabina , Morley John , Lin Chin-Teng 
Published: February 2021

AbstractObjectiveWe have designed tracking and collision prediction tasks to elucidate the differences in the physiological response to the workload variations in basic ATC tasks to untangle the impact of workload variations experienced by operators working in a complex ATC environment.BackgroundEven though several factors influence the complexity of ATC tasks, keeping track of the aircraft and preventing collision are the most crucial.MethodsPhysiological measures, such as electroencephalogram (EEG), eye activity, and heart rate variability (HRV) data, were recorded from 24 participants performing tracking and collision prediction tasks with three levels of difficulty.ResultsThe neurometrics of workload variations in the tracking and collision prediction tasks were markedly distinct, indicating that neurometrics can provide insights on the type of mental workload. The pupil size, number of blinks and HRV metric, root mean square of successive difference (RMSSD), varied significantly with the mental workload in both these tasks in a similar manner.ConclusionOur findings indicate that variations in task load are sensitively reflected in physiological signals, such as EEG, eye activity and HRV, in these basic ATC-related tasks.ApplicationThese findings have applicability to the design of future mental workload adaptive systems that integrate neurometrics in deciding not just ‘when’ but also ‘what’ to adapt. Our study provides compelling evidence in the viability of developing intelligent closed-loop mental workload adaptive systems that ensure efficiency and safety in ATC and beyond.PrécisThis article identifies the physiological correlates of mental workload variation in basic ATC tasks. The findings assert that neurometrics can provide more information on the task that contributes to the workload, which can aid in the design of intelligent mental workload adaptive system.
Hybrid multisite silicon neural probe with integrated flexible connector for interchangeable packaging
Authors: Novais Ashley , Calaza Carlos , Fernandes José , Fonseca Helder , Gaspar João , Jacinto Luis 
Published: February 2021

AbstractMultisite neural probes are a fundamental tool to study brain function. Hybrid silicon/polymer neural probes, in particular, allow the integration of complex probe geometries, such as multi-shank designs, with flexible biocompatible cabling. Despite these advantages and benefiting from the highly reproducible fabrication methods on both silicon and polymer substrates, they have not been widely available. This paper presents the development, fabrication, characterization, and in vivo electrophysiological assessment of a hybrid multisite multi-shank silicon probe with a monolithically integrated polyimide flexible interconnect cable. The fabrication process was optimized on wafer level and several neural probes with 64 gold electrode sites equally distributed along 8 shanks with an integrated 8 μm-thick highly flexible polyimide interconnect cable were produce. To avoid the time-consuming bonding of the probe to definitive packaging, the flexible cable was designed to terminate in a connector pad that can mate with commercial zero-insertion force (ZIF) connectors for electronics interfacing. This allows great experimental flexibility since interchangeable packaging can be used according to experimental demands. High-density distributed in vivo electrophysiological recordings were obtained from the hybrid neural probes with low intrinsic noise and high signal-to-noise ratio (SNR).
PDAUG - a Galaxy based toolset for peptide library analysis, visualization, and machine learning modeling
Authors: Joshi Jayadev , Blankenberg Daniel 
Published: February 2021

AbstractComputational methods based on initial screening and prediction of peptides for desired functions have been proven effective alternatives to the lengthy and expensive methods traditionally utilized in peptide research, thus saving time and effort. However, for many researchers, the lack of expertise in utilizing programming libraries and the lack of access to computational resources and flexible pipelines are big hurdles to adopting these advanced methods. To address these barriers, we have implemented the Peptide Design and Analysis Under Galaxy (PDAUG) package, a Galaxy based python powered collection of tools, workflows, and datasets for a rapid in-silico peptide library analysis. PDAUG offers tools for peptide library generation, data visualization, in-built and public database based peptide sequence retrieval, peptide feature calculation, and machine learning modeling. In contrast to the existing methods like standard programming libraries or rigid web-based tools, PDAUG offers a GUI based toolset thus providing flexibility to build and distribute reproducible pipelines and workflows without programming expertise. Additionally, this toolset facilitates researchers to combine PDAUG with hundreds of compatible existing Galaxy tools for limitless analytic strategies. Finally, we demonstrate the usability of PDAUG on predicting anticancer properties of peptides using four different feature sets and assess the suitability of various machine learning algorithms.
Redefining colorectal cancer classification and clinical stratification through a single-cell atlas
Authors: Khaliq Ateeq M. , Kurt Zeyneb , Grunvald Miles W. , Erdogan Cihat , Turgut Sevgi S. , Rand Tim , Khare Sonal , Borgia Jeffrey A. , Hayden Dana M. , Pappas Sam G. , Govekar Henry R. , Bhama Anuradha R. , Singh Ajaypal , Jacobson Richard A. , Kam Audrey E. , Zloza Andrew , Reiser Jochen , Catenacci Daniel V. , Turaga Kiran , Radovich Milan , Gupta Vineet , Al-Sabti Ram , Thyparambil Sheeno , Levy Mia A. , Subramanian Janakiraman , Kuzel Timothy M. , Sadanandam Anguraj , Hussain Arif , El-Rayes Bassel , Salahudeen Ameen A. , Masood Ashiq 
Published: February 2021

ABSTRACTColorectal cancer (CRC), a disease of high incidence and mortality, has had few treatment advances owing to a large degree of inter- and intratumoral heterogeneity. Attempts to classify subtypes of colorectal cancer to develop treatment strategies has been attempted by Consensus Molecular Subtypes (CMS) classification. However, the cellular etiology of CMS classification is incompletely understood and controversial. Here, we generated and analyzed a single-cell transcriptome atlas of 49,859 CRC cells from 16 patients, validated with an additional 31,383 cells from an independent CRC patient cohort. We describe subclonal transcriptomic heterogeneity of CRC tumor epithelial cells, as well as discrete stromal populations of cancer-associated fibroblasts (CAFs). Within CRC CAFs, we identify the transcriptional signature of specific subtypes (CAF-S1 and CAF-S4) in more than 1,500 CRC patients using bulk transcriptomic data that significantly stratifies overall survival in multiple independent cohorts. We also uncovered two CAF-S1 subpopulations, ecm-myCAF and TGFß-myCAF, known to be associated with primary resistance to immunotherapies. We demonstrate that scRNA analysis of malignant, stromal, and immune cells exhibit a more complex picture than portrayed by bulk transcriptomic-based Consensus Molecular Subtypes (CMS) classification. By demonstrating an abundant degree of heterogeneity amongst these cell types, our work shows that CRC is best represented in a transcriptomic continuum crossing traditional classification systems boundaries. Overall, this CRC cell map provides a framework to re-evaluate CRC tumor biology with implications for clinical trial design and therapeutic development.
Active Inference as a Framework for Brain-Computer Interfaces
Authors: Ather Syed Hussain 
Published: February 2021

AbstractAs Karl Friston explained during the International Symposium on Artificial Intelligence and Brain Science 2020, active inference provides a way of using abstract rule-learning and approximate Bayesian inference to show how minimizing (expected) free energy leads to active sampling of novel contingencies. Friston elaborated how there were ways of making an optimal decision using active inference that can offer perspectives to advances in artificial intelligence. These methods of optimization within the context of active inference can also be used as a framework for improving brain-computer interfaces (BCI). This way, BCIs can give rise to artificial curiosity in the way Friston had described during his session. Using Friston’s free energy principle, we can optimize the criterion a BCI uses to infer the intentions of the user from EEG observations. Under Friston’s criteria for making an optimal decision, BCIs can expand their framework of optimal decision-making using active inference.
Deep Proteome Profiling of Human Mammary Epithelia at Lineage and Age Resolution
Authors: Hinz Stefan , Manousopoulou Antigoni , Miyano Masaru , Sayaman Rosalyn W. , Aguilera Kristina Y. , Todhunter Michael E. , Lopez Jennifer C. , Sohn Lydia L. , Wang Leo D. , LaBarge Mark A. 
Published: February 2021

SUMMARYAge is the major risk factor in most carcinomas, yet little is known about how proteomes change with age in any human epithelium. We present comprehensive proteomes comprised of >9,000 total proteins, and >15,000 phosphopeptides, from normal primary human mammary epithelia at lineage resolution from ten women ranging in age from 19 to 68. Data were quality controlled, and results were biologically validated with cell-based assays. Age-dependent protein signatures were identified using differential expression analyses and weighted protein co-expression network analyses. Up-regulation of basal markers in luminal cells, including KRT14 and AXL, were a prominent consequence of aging. PEAK1 was identified as an age-dependent signaling kinase in luminal cells, which revealed a potential age-dependent vulnerability for targeted ablation. Correlation analyses between transcriptome and proteome revealed age-associated loss of proteostasis regulation. Protein expression and phosphorylation changes in the aging breast epithelium identify potential therapeutic targets for reducing breast cancer susceptibility.