bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the course of Covid-19 and other epidemic and endemic disease
Authors: Cascon Ana , Shadwick William F. 
Published: December 2021

AbstractThe Gompertz Function is an accurate model for epidemics from Cholera in 1853 to Spanish Flu in 1918 and Ebola in 2014. It also describes the acute phase of annual outbreaks of endemic influenza and in all of these instances it has significant predictive power.For Covid-19, we show that the Gompertz Function provides accurate forecasts not just for cases and deaths but, independently, for hospitalisations, intensive care admissions and other medical requirements. In particular Gompertz Function projections of healthcare requirements have been reliable enough to allow planning for: hospital admissions,intensive care admissions,ventilator usage, peak loads and duration.Analysis of data from the ‘Spanish Flu’ pandemic and the endemic influenza cycle reveals alternating periods of Gompertz Function growth and linear growth in cumulative cases or deaths. Linear growth means the Reproduction Number is equal to 1 which in turn indicates endemicity.The same pattern has been observed with Covid-19. All the initial outbreaks ended in linear growth. Each new outbreak has been preceded by a period of linear growth and has ended with a transition from Gompertz Function growth to linear growth. This suggests that each of these outbreak cycles ended with a transition to endemicity for the current dominant strain and that the normal seasonal respiratory virus periods will continue to see new outbreaks. It remains to be seen if widespread vaccination will disrupt this cyclicality.Because both Gompertz Function Growth and linear growth are accurately predictable, the forecasting problem is reduced to identifying the transition between these modes and to improving the performance in the early Gompertz Function growth phase where its predictive power is lowest.The dynamics of the Gompertz Function are determined by the Gumbel probability distribution. This is an exceptional distribution with respect to the geometry determined by the affine group on the line which is the key to the role of the Gumbel distribution as an Extreme Value Theory attractor. We show that this, together with the empirically observed asymmetry in epidemic data, makes the Gompertz Function growth essentially inevitable in epidemic models which agree with observations.
Functional implications of aging-related lncRNAs for predicting prognosis and immune status in glioma patients
Authors: Zhang Guangying , Li Yanyan , Li Na , Shen Liangfang , Li Zhanzhan 
Published: December 2021

AbstractGlioma, is the most prevalent intracranial tumor with high recurrence and mortality rate. Long noncoding RNAs (lncRNAs) play a critical role in the occurrence and progression of tumors as well as in aging regulation. Our study aimed to establish a new glioma prognosis model by integrating aging-related lncRNAs expression profiles and clinical parameters in glioma patients from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) datasets. The Pearson correlation analysis (|R|> 0.6, P<0.001) was performed to explore the aging-related lncRNAs, and univariate cox tregresion and least absolute shrinkage and selection operator (LASSO) regression were used to screening prognostic signature in glioma patients. Based on the fifteen lncRNAs, we can divide glioma patients into three subtypes, and developed a prognostic model. Kaplan-Meier survival curve analysis showed that low-risk patients had longer survival time than high-risk group. Principal component analysis indicated that aging-related lncRNAs signature had a clear distinction between high- and low-risk groups. We also found that fifteen target lncRNAs were closely correlated with 119 genes by establishing a co-expression network. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis displayed different function and pathways enrichment in high-and low-risk groups. The different missense mutations were observed in two groups, and the most frequent variant types were single nucleotide polymorphism (SNP). This study demonstrated that the novel aging-related lncRNAs signature had an important prognosis prediction and may contribute to individual treatment for glioma.
Replacement of the Gamma by the Delta variant in Brazil: impact of lineage displacement on the ongoing pandemic
Authors: Giovanetti Marta , Fonseca Vagner , Wilkinson Eduan , Tegally Houriiyah , San Emmanuel James , Althaus Christian L. , Xavier Joilson , Slavov Svetoslav Nanev , Viala Vincent Louis , Ranieri Jerônimo Lima Alex , Ribeiro Gabriela , Souza-Neto Jayme A. , Fukumasu Heidge , Coutinho Luiz Lehmann , Venancio da Cunha Rivaldo , Freitas Carla , Campelo de A e Melo Carlos F , Navegantes Wildo , do Carmo Said Rodrigo Fabiano , Almiron Maria , de Oliveira Tulio , Sampaio Sandra Coccuzzo , Elias Maria Carolina , Covas Dimas Tadeu , Holmes Edward C. , Lourenço Jose , Kashima Simone , de Alcantara Luiz Carlos Junior 
Published: December 2021

AbstractThe COVID-19 epidemic in Brazil was driven mainly by the spread of Gamma (P.1), a locally emerged Variant of Concern (VOC) that was first detected in early January 2021. This variant was estimated to be responsible for more than 96% of cases reported between January and June 2021, being associated with increased transmissibility and disease severity, a reduction in neutralization antibodies and effectiveness of treatments or vaccines, as well as diagnostic detection failure. Here we show that, following several importations predominantly from the USA, the Delta variant rapidly replaced Gamma after July 2021. However, in contrast to what was seen in other countries, the rapid spread of Delta did not lead to a large increase in the number of cases and deaths reported in Brazil. We suggest that this was likely due to the relatively successful early vaccination campaign coupled with natural immunity acquired following prior infection with Gamma. Our data reinforces reports of the increased transmissibility of the Delta variant and, considering the increasing concern due to the recently identified Omicron variant, argues for the necessity to strengthen genomic monitoring on a national level to quickly detect and curb the emergence and spread of other VOCs that might threaten global health.
Mechanically ventilated patients shed high titre live SARS-CoV2 for extended periods from both the upper and lower respiratory tract
Authors: Saud Zack , Ponsford Mark , Bentley Kirsten , Cole Jade M , Pandey Manish , Jolles Stephen , Fegan Chris , Humphreys Ian , Wise Matt P , Stanton Richard 
Published: December 2021

ABSTRACTBackgroundSARS-CoV-2 infection can lead to severe acute respiratory distress syndrome needing intensive care admission and may lead to death. As a virus that transmits by respiratory droplets and aerosols, determining the duration of viable virus shedding from the respiratory tract is critical for patient prognosis, and informs infection control measures both within healthcare settings and the public domain.MethodsWe examined upper and lower airway respiratory secretions for both viral RNA and infectious virions in mechanically ventilated patients admitted to the intensive care unit of the University Hospital of Wales. Samples were taken from the oral cavity (saliva), oropharynx (sub-glottic aspirate), or lower respiratory tract (non-directed bronchoalveolar lavage (NBL) or bronchoalveolar lavage (BAL)) and analyzed by both qPCR and plaque assay.Results117 samples were obtained from 25 patients. qPCR showed extremely high rates of positivity across all sample types, however live virus was far more common in saliva (68%) than in BAL/NBAL (32%). Average titres of live virus were higher in subglottic aspirates (4.5×107) than in saliva (2.2×106) or BAL/NBAL (8.5×106), and reached >108PFU/ml in some samples. The longest duration of shedding was 98 days, while the majority of patients (14/25) shed live virus for 20 days or longer.ConclusionsIntensive care unit patients infected with SARS-CoV-2 can shed high titres of virus both in the upper and lower respiratory tract, and tend to be prolonged shedders. This information is important for decision making around cohorting patients, de-escalation of PPE, and undertaking potential aerosol generating procedures.SummaryPatients on intensive therapy infected with SARS-CoV-2 tend to be prolonged shedders, excreting virus for far beyond the time periods specified in current guidelines, and live virus titres can be extremely high in both the upper and lower respiratory tracts.
Immunogenicity of heterologous BNT162b2 booster in fully vaccinated individuals with CoronaVac against SARS-CoV-2 variants Delta and Omicron: the Dominican Republic Experience
Authors: Pérez-Then Eddy , Lucas Carolina , Monteiro Valter Silva , Miric Marija , Brache Vivian , Cochon Leila , Vogels Chantal B. F. , De la Cruz Elena , Jorge Aidelis , De los Santos Margarita , Leon Patricia , Breban Mallery I. , Billig Kendall , Yildirim Inci , Pearson Claire , Downing Randy , Gagnon Emily , Muyombwe Anthony , Razeq Jafar , Campbell Melissa , Ko Albert , Omer Saad B. , Grubaugh Nathan D. , Vermund Sten H. , Iwasaki Akiko 
Published: December 2021

AbstractThe recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and by its numerous spike mutations with potential to evade neutralizing antibodies elicited by COVID-19 vaccines. The Dominican Republic was among the first countries in recommending the administration of a third dose COVID-19 vaccine to address potential waning immunity and reduced effectiveness against variants. Here, we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants that had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that heterologous CoronaVac prime followed by BNT162b2 booster regimen induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and Delta variant, resembling the titers obtained after two doses of mRNA vaccines. While neutralization of Omicron was undetectable in participants that had received a two-dose regimen of CoronaVac vaccine, BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron, compared to two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 6.3-fold and 2.7-fold for Omicron compared to ancestral and Delta variant, respectively. Surprisingly, previous SARS-CoV-2 infection did not affect the neutralizing titers for Omicron in participants that received the heterologous regimen. Our findings have immediate implications for multiples countries that previously used a two-dose regimen of CoronaVac and reinforce the notion that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.
Testing for genetic assimilation with phylogenetic comparative analysis: Conceptual, methodological, and statistical considerations
Authors: Gunderson Alex R. , Revell Liam J. 
Published: December 2021

AbstractGenetic assimilation is a process that leads to reduced phenotypic plasticity during adaptation to novel conditions, a potentially important phenomenon under global environmental change. Null expectations when testing for genetic assimilation, however, are not always clear. For instance, the statistical artifact of regression to the mean could bias us towards detecting genetic assimilation when it has not occurred. Likewise, the specific mechanism underlying plasticity expression may affect null expectations under neutral evolution. We used macroevolutionary numerical simulations to examine both of these important issues and their interaction, varying whether or not plasticity evolves, the evolutionary mechanism, trait measurement error, and experimental design. We also modified an existing reaction norm correction method to account for phylogenetic non-independence. We found: 1) regression to the mean is pervasive and can generate spurious support for genetic assimilation; 2) experimental design and post-hoc correction can minimize this spurious effect; and 3) neutral evolution can produce patterns consistent with genetic assimilation without constraint or selection, depending on the mechanism of plasticity expression. Additionally, we re-analyzed published macroevolutionary data supporting genetic assimilation, and found that support was lost after proper correction. Considerable caution is thus required whenever investigating genetic assimilation and reaction norm evolution at macroevolutionary scales.
A meta-analysis of task-based differences in bilingual L1 and L2 language networks
Authors: Comstock Lindy , Oliver Bruce 
Published: December 2021

AbstractThe functional organization of first (L1) and second (L2) language processing in bilinguals remains a topic of great interest to the neurolinguistics community. Functional magnetic resonance imaging (fMRI) studies report meaningful differences in the location and extent of hemodynamic changes between tasks performed in the L1 and L2, yet there is no consensus on whether these networks can be considered truly distinct. In part, this may be due to the multiplicity of task designs implemented in such studies, which complicates the interpretation of their findings. This paper compares the results of previous bilingual meta-analyses to a new ALE meta-analysis that categorizes neuroimaging studies by task design. Factors such as the age of L2 acquisition (AoA) and the L2 language proficiency level of participants are also considered. The findings support previous accounts of the effect of participant characteristics on linguistic processing, while at the same time revealing dissociable differences in fMRI activation for L1 and L2 networks within and across tasks that appear independent of these external factors.
Screening of Chimeric GAA Variants in a Preclinical Study of Pompe Disease Results in Candidate Vector for Hematopoietic Stem Cell Gene Therapy
Authors: Dogan Yildirim , Barese Cecilia N. , Schindler Jeffrey W. , Yoon John K. , Unnisa Zeenath , Guda Swaroopa , Jacobs Mary E. , Oborski Christine , Clarke Diana L. , Schambach Axel , Pfeifer Richard , Harper Claudia , Mason Chris , van Til Niek P. 
Published: December 2021

AbstractPompe disease is a rare genetic neuromuscular disorder caused by acid alpha-glucosidase (GAA) deficiency resulting in lysosomal glycogen accumulation and progressive myopathy. Enzyme replacement therapy (ERT) is the current standard of care, which prolongs the quality of life for Pompe patients. However, ERT has limitations due to lack of enzyme penetration into the central nervous system (CNS) and skeletal muscles, immunogenicity against the recombinant enzyme, and requires life-long biweekly infusions. In a preclinical mouse model, a clinically relevant promoter to drive lentiviral vector-mediated expression of engineered GAA in autologous hematopoietic stem and progenitor cells (HSPC) was tested with nine unique human chimeric GAA coding sequences incorporating distinct peptide tags and codon-optimization iterations. Vectors including glycosylation independent lysosomal targeting (GILT) tags resulted in effective GAA enzyme delivery into key disease tissues with enhanced reduction of glycogen, myofiber and CNS vacuolation, compared to non-tagged GAA in Gaa knockout mice, a model of Pompe disease. Genetically modified microglial cells in brains were detected at low levels, but provided robust correction. Furthermore, an aminoacid substitution in the tag added to reduced capacity to induce insulin signaling and there was no evidence of off-target effects. This study demonstrated the therapeutic potential of lentiviral HSPC gene therapy exploiting optimized GAA tagged coding sequences to reverse Pompe disease pathology in a preclinical mouse model providing a promising vector candidate for further investigation.One Sentence SummaryA candidate vector for hematopoietic stem cell gene therapy of Pompe disease.
Evidence of learning walks related to scorpion home burrow navigation
Authors: Gaffin Douglas D. , Muñoz Maria G. , Hoefnagels Mariëlle 
Published: December 2021

ABSTRACTTheNavigation by Chemotextural Familiarity Hypothesis(NCFH) suggests that scorpions use their midventral pectines to gather chemical and textural information near their burrows and use this information as they subsequently return home. For NCFH to be viable, animals must somehow acquire home-directed “tastes” of the substrate, such as through path integration (PI) and/or learning walks. We conducted laboratory behavioral trials using desert grassland scorpions (Paruroctonus utahensis). Animals reliably formed burrows in small mounds of sand we provided in the middle of circular, sandlined behavioral arenas. We processed overnight infrared video recordings with a MATLAB script that tracked animal movements at 1-2 s intervals. In all, we analyzed the movements of 23 animals, representing nearly 1500 hours of video recording. We found that once animals established their home burrows, they immediately made one to several short, looping excursions away from and back to their burrows before walking greater distances. We also observed similar excursions when animals made burrows in level sand in the middle of the arena (i.e., no mound provided). These putative learning walks, together with recently reported PI in scorpions, may provide the crucial home-directed information requisite for NCFH.
A single cell transcriptional roadmap for human pacemaker cell differentiation
Authors: Wiesinger Alexandra , Li Jiuru , Fokkert Lianne , Bakker Priscilla , Verkerk Arie O. , Christoffels Vincent M. , Boink Gerard J.J. , Devalla Harsha D. 
Published: December 2021

AbstractEach heartbeat is triggered by the sinoatrial node, the natural pacemaker of the heart. Animal models have revealed that pacemaker cells share a common progenitor with the (pro)epicardium, and that the pacemaker cardiomyocytes further diversify into “transitional”, “tail” and “head” subtypes. However, the underlying molecular mechanisms are poorly understood. Here, we studied the differentiation of human induced pluripotent stem cells into pacemaker cardiomyocytes. Single cell RNA sequencing identified the presence of myocardial populations resembling subtypes present in the formed sinoatrial node, and in addition revealed a side population of (pro)epicardial cells. Time-course trajectory analysis uncovered a role for WNT signaling in determining myocardial versus proepicardial cell fate. We experimentally demonstrate that presence of WNT signaling prior to the branching point of a common progenitor enhances proepicardial cell differentiation at the expense of myocardial pacemaker cells. Furthermore, we uncover a role for TGFβ and WNT signaling in differentiation towards transitional and head pacemaker subtypes, respectively. Our findings provide new biological insights into human pacemaker differentiation, open avenues for complex disease modeling and inform regenerative approaches.
Interleukin 4 controls the role of macrophages in pulmonary metastatic tumor cell seeding and growth
Authors: Rodriguez-Tirado Carolina , Entenberg David , Li Jiufeng , Qian Bin-Zhi , Condeelis John S. , Pollard Jeffrey W 
Published: December 2021

AbstractMetastasis is the systemic manifestation of cancer and the main cause of death from breast cancer. In mouse models of lung metastases, recruitment of classical monocytes from blood to the lung and their differentiation to metastasis-associated macrophages (MAMs) facilitate cancer cell extravasation, survival, and growth. Ablation of MAMs or their monocytic progenitors inhibits metastasis. We hypothesized that factors controlling macrophage polarization modulate tumor cell extravasation in the lung. We evaluated whether signaling by Th1 or Th2 cytokines in macrophages affected trans-endothelial migration of tumor cells in vitro. Interferon γ and LPS inhibited macrophage-dependent tumor cell extravasation while the Th2 cytokine interleukin-4 (IL4) enhanced this process. We demonstrated that IL4 receptor (IL4rα)null mice develop fewer and smaller lung metastasis. Adoptive transfer of wild type monocytes toIL4rαdeficient mice rescued this phenotype. IL4 signaling in macrophages controls the expression of the chemokine receptor CXCR2, necessary for IL4-mediated tumor cell extravasation in vitro. Furthermore, IL4 signaling in macrophages transcriptionally regulates several other genes already causally associated with lung metastasis including CCL2, CSF1, CCR1, HGF and FLT1. The central role for IL4 signaling in MAMs was confirmed by high-resolution intravital imaging of the lung in mice at the time of metastatic seeding, which showed reduced physical interaction between tumor cells andIL4rα-deficient macrophages. This interaction enhances tumor cell survival. These data indicate that IL4 signaling in monocytes and macrophages is key during seeding and growth of breast metastasis in the lung as it regulates pro-tumoral paracrine signaling between cancer cells and macrophages.
Evaluation of chest X-Ray with automated interpretation algorithms for mass tuberculosis screening in prisons
Authors: Soares Thiego Ramon , de Oliveira Roberto Dias , Liu Yiran E. , Silva Santos Andrea da , Santos Paulo Cesar Pereira dos , Monte Luma Ravena Soares , Oliveira Lissandra Maia de , Park Chang Min , Hwang Eui Jin , Andrews Jason R. , Croda Julio 
Published: December 2021

ABSTRACTRationaleThe World Health Organization (WHO) recommends systematic tuberculosis (TB) screening in prisons. Evidence is lacking for accurate and scalable screening approaches in this setting.ObjectivesTo assess the diagnostic accuracy of artificial intelligence-based chest x-ray interpretation algorithms for TB screening in prisons.MethodsProspective TB screening study in three prisons in Brazil from October 2017 to December 2019. We administered a standardized questionnaire, performed chest x-ray in a mobile unit, and collected sputum for confirmatory testing using Xpert MTB/RIF and culture. We evaluated x-ray images using three algorithms (CAD4TB version 6, LunitTB and qXR) and compared their diagnostic accuracy. We utilized multivariable logistic regression to assess the effect of demographic and clinical characteristics on algorithm accuracy. Finally, we investigated the relationship between abnormality scores and Xpert semi-quantitative results.Measurements and Main ResultsAmong 2,075 incarcerated individuals, 259 (12.5%) had confirmed TB. All three algorithms performed similarly overall with AUCs of 0.87-0.91. At 90% sensitivity, only LunitTB and qXR met the WHO Target Product Profile requirements for a triage test, with specificity of 84% and 74%, respectively. All algorithms had variable performance by age, prior TB, smoking, and presence of TB symptoms. LunitTB was the most robust to this heterogeneity, but nonetheless failed to meet the TPP for individuals with previous TB. Abnormality scores of all three algorithms were significantly correlated with sputum bacillary load.ConclusionsAutomated x-ray interpretation algorithms can be an effective triage tool for TB screening in prisons. However, their specificity is insufficient in individuals with previous TB.