bluuebunny/crossref_metadata_2025_split huggingface dataset:
A kinetic model considering the decline of antibody level and vaccination of COVID-19
Authors: Xu Chuanqing , Huang Xiaotong , Zhang Zonghao , Cui Jingan 
Published: December 2021

AbstractIn order to evaluate the decline in antibody levels and the impact of vaccination on the spread of the epidemic, we establish COVID-19 dynamic models that consider the decline in antibody levels and the effects of vaccination, and retrospectively evaluate the epidemic situation in England. Based on the epidemic data in England from September 1 to October 31, 2020, considering the continuous decline in the antibody level of COVID-19 recovers, an improved SEIR infectious disease dynamics model that considers the reinfection of recovers due to the decline in antibody levels is established. The kinetic parameters of the SEIR model are obtained by fitting. On this basis, a SEIRV infectious disease dynamic model with vaccination is established to study the impact of different vaccination rates and vaccine failure rates on the development of the epidemic in England. We obtain the lower the vaccine failure rate, the fewer new cases. When the vaccination rate is fixed at 0.005 (equivalent to 250000 people vaccinated every day), the peak of the epidemic will decrease with the decrease of vaccine failure rate. The peak value when the failure rate is 0.001 is 81.4% lower than the peak value when the failure rate is 0.01, and the peak value when the failure rate is 0.01 is 89.5% lower than the peak value when the failure rate is 0.02. When the failure rate is less than 0.01, the peak time will advance with the decrease of failure rate; when the failure rate is greater than 0.01, the peak time will be delayed with the decrease of failure rate; when the failure rate is 0.01, the peak time is 528 days later than that when the failure rate is 0.001 and 295 days later than that when the failure rate is 0.05. On the 60th day of vaccination, the vaccine failure rate of 0.002 decreases the number of cases by 5.8% compared with the vaccine failure rate of 0.01; on the 70th day of vaccination, the vaccine failure rate of 0.002 reduces the number of cases by 9.1% compared with the vaccine failure rate of 0.01. Therefore, with the extension of time, the vaccine with low failure rate has a more obvious effect on reducing the number of cases than the vaccine with high failure rate. When the vaccine failure rate is fixed at 0.005, we study the impact of different vaccination rates on the spread of the epidemic in England, the result shows that the peak of epidemic situation decreases with the increase of vaccination rate, and the peak time advance with the increase of vaccination rate, when the vaccination rate is 0.025, the peak decreases by 74.8% and the peak time was 114 days earlier than that when the vaccination rate is 0.005. Therefore, the higher the vaccine efficiency and vaccination rate, the lower the peak of the epidemic. On the basis of improving the effectiveness of vaccines, increasing the vaccination rate is of practical significance for controlling the spread of the epidemic.
A multicentre, prospective, randomised controlled trial to evaluate hexaminolevulinate photodynamic therapy (Cevira®) as a novel treatment in patients with high grade squamous intraepithelial lesion: APRICITY Phase 3 study protocol
Authors: Chen Fei , Novák Zoltán , Dannecker Christian , Sui Long , Zhang Youzhong , You Zhixue , Han Ling , Lang Jinghe , Hillemanns Peter 
Published: December 2021

AbstractIntroductionHigh-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality.ObjectiveAPRICITY is a multicentre, prospective, double-blind, randomised controlled Phase 3 study further evaluating the efficacy and safety of Cevira®, an integrated drug- and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive therapy for women with HSIL.Methods and analysisPatients with biopsy-confirmed HSIL histology are invited to participate in the study currently being conducted at 47 sites in China and 25 sites in Ukraine, Russia and European Union. The aim is to include at least 384 patients which will be randomised to either Cevira® or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low grade squamous intraepithelial lesion (LSIL). Primary endpoint is the proportion of the responders at 6 months after first treatment. Secondary efficacy endpoints and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints for Cevira® device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira® group will be enrolled in an open, long-term extension study following patients for further 6 months to collect additional efficacy and safety data (study extension endpoints).ConclusionDue to its non-invasiveness and convenient application, Cevira® may be a favourable alternative to surgical methods in treatment of patients with HSIL.Ethics and disseminationThe study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations.Trial registration numberclinicaltrials.govNCT04484415
COVID-19 infections post-vaccination by HIV status in the United States
Authors: Coburn Sally B. , Humes Elizabeth , Lang Raynell , Stewart Cameron , Hogan Brenna C , Gebo Kelly A. , Napravnik Sonia , Edwards Jessie K. , Browne Lindsay E. , Park Lesley S. , Justice Amy C. , Gordon Kirsha , Horberg Michael A. , Certa Julia M. , Watson Eric , Jefferson Celeena R , Silverberg Michael , Skarbinski Jacek , Leyden Wendy A , Williams Carolyn F. , Althoff Keri N. ,   for the Corona-Infectious-Virus Epidemiology Team (CIVETs) of the NA-ACCORD of IeDEA
Published: December 2021

ABSTRACTImportanceRecommendations for additional doses of COVID vaccine are restricted to people with HIV who have advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk post-vaccination among PWH is essential for informing vaccination guidelines.ObjectiveEstimate the risk of breakthrough infections among fully vaccinated people with (PWH) and without (PWoH) HIV in the US.Design, setting, and participantsThe Corona-Infectious-Virus Epidemiology Team (CIVET)-II cohort collaboration consists of 4 longitudinal cohorts from integrated health systems and academic health centers. Each cohort identified individuals ≥18 years old, in-care, and fully vaccinated for COVID-19 through 30 June 2021. PWH were matched to PWoH on date fully vaccinated, age group, race/ethnicity, and sex at birth. Incidence rates per 1,000 person-years and cumulative incidence of breakthrough infections with 95% confidence intervals ([,]) were estimated by HIV status. Cox proportional hazards models estimated adjusted hazard ratios (aHR) of breakthrough infections by HIV status adjusting for demographic factors, prior COVID-19 illness, vaccine type (BNT162b2, [Pfizer], mRNA-1273 [Moderna], Jansen Ad26.COV2.S [J&J]), calendar time, and cohort. Risk factors for breakthroughs among PWH, were also investigated.ExposureHIV infectionOutcomeCOVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after an individual was fully vaccinated.ResultsAmong 109,599 individuals (31,840 PWH and 77,759 PWoH), the rate of breakthrough infections was higher in PWH versus PWoH: 44 [41, 48] vs. 31 [29, 33] per 1,000 person-years. Cumulative incidence at 210 days after date fully vaccinated was low, albeit higher in PWH versus PWoH overall (2.8% versus 2.1%, log-rank p<0.001, risk difference=0.7% [0.4%, 1.0%]) and within each vaccine type. Breakthrough infection risk was 41% higher in PWH versus PWoH (aHR=1.41 [1.28, 1.56]). Among PWH, younger age (18-24 versus 45-54), history of COVID-19 prior to fully vaccinated date, and J&J vaccination (versus Pfizer) were associated with increased risk of breakthroughs. There was no association of breakthrough with HIV viral load suppression or CD4 count among PWH.Conclusions and RelevanceCOVID-19 vaccination is effective against infection with SARS-CoV-2 strains circulating through 30 Sept 2021. PWH have an increased risk of breakthrough infections compared to PWoH. Recommendations for additional vaccine doses should be expanded to all PWH.
KAGE: Fast alignment-free graph-based genotyping of SNPs and short indels
Authors: Grytten Ivar , Rand Knut Dagestad , Sandve Geir Kjetil 
Published: December 2021

AbstractGenotyping is a core application of high-throughput sequencing. We present KAGE, a genotyper for SNPs and short indels that is inspired by recent developments within graph-based genome representations and alignment-free methods. KAGE uses a pan-genome representation of the population to efficiently and accurately predict genotypes. Two novel ideas improve both the speed and accuracy: a Bayesian model incorporates genotypes from thousands of individuals to improve prediction accuracy, and a computationally efficient method leverages correlation between variants. We show that the accuracy of KAGE is at par with the best existing alignment-free genotypers, while being an order of magnitude faster.
Enhancing Quantitative and Data Science Education for Graduate Students in Biomedical Science
Authors: Gross Louis J. , McCord Rachel Patton , LoRe Sondra , Ganusov Vitaly V. , Hong Tian , Strickland W. Christopher , Talmy David , Arnim Albrecht G. von , Wiggins Greg 
Published: December 2021

AbstractSubstantial guidance is available on undergraduate quantitative training for biologists, including reports focused on biomedical science, but far less attention has been paid to the graduate curriculum. In this setting, we propose an innovative approach to quantitative education that goes beyond recommendations of a course or set of courses or activities. Due to the diversity of quantitative methods, it is infeasible to expect that biomedical PhD students can be exposed to more than a minority of the quantitative concepts and techniques employed in modern biology. We developed a novel prioritization approach in which we mined and analyzed quantitative concepts and skills from publications that faculty in relevant units deemed central to the scientific comprehension of their field. The analysis provides a prioritization of quantitative skills and concepts and could represent an effective method to drive curricular focus based upon program-specific faculty input for biological science programs of all types. Our results highlight the disconnect between typical undergraduate quantitative education for life science students, focused on continuous mathematics, and the concepts and skills in graphics, statistics, and discrete mathematics that arise from priorities established by biomedical science faculty.One Sentence SummaryWe developed a novel approach to prioritize quantitative concepts and methods for inclusion in a graduate biomedical science curriculum based upon approaches included in faculty-identified key publications.
Quantifying the Invasive Secondary Metabolome
Authors: Rowland-Chandler Jamila , Salter Ewan , Babu Suresh , Yadav Gitanjali 
Published: December 2021

AbstractInvasive plants drive ecosystem degradation through developing aggressive phenotypes that can outcompete native flora. Several hypotheses explain this, like the Evolution of Increased Competitive Ability hypothesis and the Novel Weapons Hypothesis, but none have been proven conclusively. Changes in plant metabolites are critical to these hypotheses, but complete invasive secondary metabolomes have not been quantified. Here, statistical and unsupervised machine-learning approaches were used to analyse chemotype-to-phenotype relationships in invasive and non-invasive populations in species Ageratum conyzoides, Lantana camara, Melaleuca quinquenervia and Psidium cattleainum and on a family level analysing Asteraceae, Myrtaceae and Verbenaceae. Invasive metabolomes evolved according to the EICA and NWH, involving optimisation of aggressive strategies present in native populations and local adaptation.Abstract Figure
Intraspecific variation in migration timing of green sturgeon in the Sacramento River system
Authors: Colborne Scott F. , Sheppard Lawrence W. , O’Donnell Daniel R. , Reuman Daniel C. , Walter Jonathan A. , Singer Gabriel P. , Kelly John T. , Thomas Michael J. , Rypel Andrew L. 
Published: December 2021

AbstractBackgroundUnderstanding movement patterns of anadromous fishes is critical to conservation management of declining wild populations and preservation of habitats. Yet, infrequent observations of individual animals fundamentally constrain accurate descriptions of movement dynamics.MethodsIn this study, we synthesized over a decade (2006–2018) of acoustic telemetry tracking observations of green sturgeon (Acipenser medirostris) in the Sacramento River system to describe major anadromous movement patterns.ResultsWe observed that green sturgeon exhibited a unimodal in-migration during the spring months but had a bimodal distribution of out-migration timing, split between an ‘early’ out-migration (32%) group during May - June, or alternatively, holding in the river until a ‘late’ out-migration (68%), November - January. Focusing on these out-migration groups, we found that river discharge, but not water temperature, may cue the timing of migration, and that fish showed a tendency to maintain out-migration timing between subsequent spawning migration events.ConclusionsWe recommend that life history descriptions of green sturgeon in this region reflect the distinct out-migration periods described here. Furthermore, we encourage the continued use of biotelemetry to describe migration timing and life history variation, not only this population but other green sturgeon populations and other species.
Reduced Dimension, Biophysical Neuron Models Constructed From Observed Data
Authors: Clark Randall , Fuller Lawson , Platt Jason A. , Abarbanel Henry D. I. 
Published: December 2021

AbstractUsing methods from nonlinear dynamics and interpolation techniques from applied mathematics, we show how to use data alone to construct discrete time dynamical rules that forecast observed neuron properties. These data may come from from simulations of a Hodgkin-Huxley (HH) neuron model or from laboratory current clamp experiments. In each case the reduced dimension data driven forecasting (DDF) models are shown to predict accurately for times after the training period.When the available observations for neuron preparations are, for example, membrane voltage V(t) only, we use the technique of time delay embedding from nonlinear dynamics to generate an appropriate space in which the full dynamics can be realized.The DDF constructions are reduced dimension models relative to HH models as they are built on and forecast only observables such as V(t). They do not require detailed specification of ion channels, their gating variables, and the many parameters that accompany an HH model for laboratory measurements, yet all of this important information is encoded in the DDF model.As the DDF models use only voltage data and forecast only voltage data, they can be used in building networks with biophysical connections. Both gap junction connections and ligand gated synaptic connections among neurons involve presynaptic voltages and induce postsynaptic voltage response. Biophysically based DDF neuron models can replace other reduced dimension neuron models, say of the integrate-and-fire type, in developing and analyzing large networks of neurons.When one does have detailed HH model neurons for network components, a reduced dimension DDF realization of the HH voltage dynamics may be used in network computations to achieve computational efficiency and the exploration of larger biological networks.
Why do hippocampal mossy cells matter? It depends on the frequency and context
Authors: Kolaric Katarina , Strauch Christina , Li Yingxin , Woods Sasha , Lopes Marinho A. , Sivarajah Natasha , Teixeira Catia M. , Lerch Jason , Frankland Paul W. , Henkelman Mark , Bortolotto Zuner A , Clea Warburton E. , Bashir Zafar I , Manahan-Vaughan Denise , Atan Denize 
Published: December 2021

AbstractThe discrimination of similar episodes and places, and their representation as distinct memories, depend on a process called pattern separation that relies on the circuitry of the hippocampal dentate gyrus (DG). Mossy cells (MCs) are key neurons in the circuitry, but how they influence DG network dynamics, function, and seizure risk has not been fully elucidated. We found the net impact of MCs was inhibitory at physiological frequencies connected with learning and behaviour, and their absence associated with deficits in pattern separation and spatial memory; at higher frequencies, their net impact was excitatory, and their absence protected against seizures. Thus, MCs influence DG outputs in a highly dynamic manner that varies with frequency and context.One-Sentence SummaryHippocampal mossy cells are required for learning and memory; but their absence protects against seizures.
Sterilization of drug-resistant influenza virus through genetic interference: use of unnatural amino acid-engineered virions
Authors: Wu Xuesheng , Zheng Zhetao , Chen Hongmin , Lin Haishuang , Yang Yuelin , Bai Yachao , Xia Qing 
Published: December 2021

AbstractThe frequent emergence of drug resistance during the treatment of influenza A virus (IAV) infections highlights a need for effective antiviral countermeasures. Here, we present an antiviral method that utilizes unnatural amino acid-engineered drug-resistant (UAA-DR) virus. The engineered virus is generated through genetic code expansion to combat emerging drug-resistant viruses. The UAA-DR virus has unnatural amino acids incorporated into its drug-resistant protein and its polymerase complex for replication control. The engineered virus can undergo genomic segment reassortment with normal virus and produce sterilized progenies due to artificial amber codons in the viral genome. We validate in vitro that UAA-DR can provide a broad-spectrum antiviral strategy for several H1N1 strains, different DR-IAV strains, multidrug-resistant (MDR) strains, and even antigenically distant influenza strains (e.g., H3N2). Moreover, a minimum dose of neuraminidase (NA) inhibitors for influenza virus can further enhance the sterilizing effect when combating inhibitor-resistant strains, partly due to the promoted superinfection of unnatural amino acid-modified virus in cellular and animal models. We also exploited the engineered virus to achieve adjustable efficacy after external UAA administration, for mitigating DR virus infection on transgenic mice harboring the pair, and to have substantial elements of the genetic code expansion technology, which further demonstrated the safety and feasibility of the strategy. We anticipate that the use of the UAA-engineered DR virion, which is a novel antiviral agent, could be extended to combat emerging drug-resistant influenza virus and other segmented RNA viruses.
Role of oxidation of excitation-contraction coupling machinery in age-dependent loss of muscle function in C. elegans
Authors: Dridi Haikel , Forrester Frances , Umanskaya Alisa , Xie Wenjun , Reiken Steven , Lacampagne Alain , Marks Andrew R. 
Published: December 2021

ABSTRACTAge-dependent loss of body wall muscle function and impaired locomotion occur within 2 weeks in C. elegans; however, the underlying mechanism has not been fully elucidated. In humans, age-dependent loss of muscle function occurs at about 80 years of age and has been linked to dysfunction of ryanodine receptor (RyR)/intracellular calcium (Ca2+) release channels on the sarcoplasmic reticulum (SR). Mammalian skeletal muscle RyR1 channels undergo age-related remodeling due to oxidative overload, leading to loss of the stabilizing subunit calstabin1 (FKBP12) from the channel macromolecular complex. This destabilizes the closed state of the channel resulting in intracellular Ca2+ leak, reduced muscle function, and impaired exercise capacity. We now show that the C. elegans RyR homolog, UNC-68, exhibits a remarkable degree of evolutionary conservation with mammalian RyR channels and similar age-dependent dysfunction. Like RyR1 in mammals UNC-68 encodes a protein that comprises a macromolecular complex which includes the calstabin1 homolog FKB-2 and is immunoreactive with antibodies raised against the RyR1 complex. Further, as in aged mammals, UNC-68 is oxidized and depleted of FKB-2 in an age-dependent manner, resulting in “leaky” channels, depleted SR Ca2+ stores, reduced body wall muscle Ca2+ transients, and age-dependent muscle weakness. FKB-2 (ok3007)-deficient worms exhibit reduced exercise capacity. Pharmacologically induced oxidization of UNC-68 and depletion of FKB-2 from the channel independently caused reduced body wall muscle Ca2+ transients. Preventing FKB-2 depletion from the UNC-68 macromolecular complex using the Rycal drug S107 improved muscle Ca2+ transients and function. Taken together, these data suggest that UNC-68 oxidation plays a role in age-dependent loss of muscle function. Remarkably, this age-dependent loss of muscle function induced by oxidative overload, which takes ~2 years in mice and ~80 years in humans, occurs in less than 2-3 weeks in C. elegans, suggesting that reduced anti-oxidant capacity may contribute to the differences in life span amongst species.
LungMAP Portal Ecosystem: Systems-Level Exploration of the Lung
Authors: Gaddis Nathan , Fortriede Joshua , Guo Minzhe , Bardes Eric E. , Kouril Michal , Tabar Scott , Burns Kevin , Ardini-Poleske Maryanne E. , Loos Stephanie , Schnell Daniel , Jin Kang , Iyer Balaji , Du Yina , Korte Jeff , Munshi Ruchi , Smith Victoria , Herbst Andrew , Kitzmiller Joseph A. , Clair Geremy C. , Carson James , Adkins Joshua , Morrisey Edward E. , Pryhuber Gloria S. , Misra Ravi , Whitsett Jeffrey A. , Sun Xin , Heathorn Trevor , Paten Benedict , Surya Prasath V. B. , Xu Yan , Tickle Tim , Aronow Bruce J. , Salomonis Nathan ,   NHLBI LungMAP Consortium
Published: December 2021

ABSTRACTAn improved understanding of the human lung necessitates advanced systems models informed by an ever-increasing repertoire of molecular omics, cellular, imaging and pathological datasets. To centralize and standardize information across broad lung research efforts we expanded the LungMAP.net website into a gateway portal. This portal connects a broad-spectrum of research networks, bulk and single-cell multi-omics data and a diverse collection of image data that span mammalian lung development and disease. The data are standardized across species and technologies using harmonized data and metadata models that leverage recent advances including those from the Human Cell Atlas, diverse ontologies, and the LungMAP CellCards initiative. To cultivate future discoveries, we have aggregated a diverse collection of single-cell atlases for multiple species (human, rhesus, mouse), to enable consistent queries across technologies, cohorts, age, disease and drug treatment. These atlases are provided as independent and integrated queriable datasets, with an emphasis on dynamic visualization, figure generation and reference-based classification of user-provided datasets (Azimuth). As this resource grows, we intend to increase the breadth of available interactive interfaces, data portals and datasets from LungMAP and external research efforts.