bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmunity to the Lung Protective Phospholipid-Binding Protein Annexin A2 Predicts Mortality Among Hospitalized COVID-19 Patients
Authors: Zuniga Marisol , Gomes Claudia , Carsons Steven E. , Bender Michael T. , Cotzia Paolo , Miao Qing Robert , Lee David C. , Rodriguez Ana 
Published: January 2021

ABSTRACTBackgroundAnnexin A2 is a phospholipid-binding protein involved in fibrinolysis, cell membrane stabilization and repair, and ensuring the integrity of the pulmonary microvasculature. Given the autoantibodies observed in COVID-19 and that Annexin A2 is a known target of antiphospholipid antibodies, we studied autoimmunity directed against Annexin A2 among hospitalized COVID-19 patients.MethodsWe used ELISA to identify the levels of IgG autoantibodies recognizing Annexin A2 and A5 among 86 hospitalized cases of COVID-19. Using logistic regression, we analyzed the association between anti-Annexin A2 and A5 antibody levels with mortality after adjusting for age, sex, race and key comorbidities.ResultsWe found higher average levels of anti-Annexin A2 antibodies among hospitalized COVID-19 patients that died when compared with non-critical hospitalized COVID-19 patients (p-value = 0.006) and critically ill COVID-19 patients (p-value = 0.04). No significant differences in anti-Annexin A5 antibody levels were identified. Regression analysis showed that anti-Annexin A2 antibody levels as measured in relative units strongly predicted mortality with an odds ratio of 9.3 (95% CI: 1.9 to 44.6, p=0.005). In contrast, anti-Annexin A5 antibody levels were not associated with higher mortality (95% CI: 0.5 to 15.2, p=0.22).ConclusionsWe determined that anti-Annexin A2 antibodies were elevated among hospitalized COVID-19 patients and these levels predicted mortality. It is known that inhibition of Annexin A2 induces systemic thrombosis, cell death, and non-cardiogenic pulmonary edema. Autoimmunity to Annexin A2 is a potential mechanism that may explain the key clinical findings of severe COVID-19.
An in-depth analysis of phosphorylated tau in amyotrophic lateral sclerosis post-mortem motor cortex and cerebrospinal fluid
Authors: Petrozziello Tiziana , Amaral Ana C. , Dujardin Simon , Farhan Sali M.K. , Chan James , Trombetta Bianca A. , Kivisäkk Pia , Mills Alexandra N. , Bordt Evan A. , Kim Spencer E. , Dooley Patrick M. , Ghosal Anubrata , Gomez-Isla Teresa , Hyman Bradley T. , Arnold Steven E. , Spires-Jones Tara , Cudkowicz Merit E. , Berry James D. , Sadri-Vakili Ghazaleh 
Published: January 2021

AbstractAlthough the molecular mechanisms underlying amyotrophic lateral sclerosis (ALS) are not yet fully understood, recent studies have described alterations in tau protein in both sporadic and familial ALS. However, it is unclear whether alterations in tau contribute to ALS pathogenesis. Here, we leveraged the ALS Knowledge Portal and Project MinE data sets and identified specific genetic variants clustering within the microtubule-binding domain of MAPT, which were unique to ALS cases. Furthermore, our analysis in a large post-mortem cohort of ALS and control motor cortex demonstrates that although there was no significant difference in the presence of phosphorylated tau (pTau) neuropil threads and neurofibrillary tangles between the two groups, pTau-S396 and pTau-S404 mis-localized to the nucleus and synapses in ALS. This was specific to the C-terminus phosphorylation sites as there was a significant decrease in pTau-T181 in ALS synaptoneurosomes compared to controls. Lastly, while there was no change in total tau or pTau-T181 in ALS CSF, there was a decrease in pTau-T181:tau ratio in ALS CSF, as previously reported. Importantly, CSF tau levels were increased in ALS patients diagnosed with bulbar onset ALS, while pTau-T181:tau ratio was decreased in ALS patients diagnosed with both bulbar and limb onset. Additionally, there was an inverse correlation between tau levels in the CSF and the revised ALS functional rating scale (ALSFRS-R) as well as a correlation between pTau-T181:tau ratio and ALSFRS-R. While there were no longitudinal alterations in tau, pTau-T181 and pTau-T181:tau ratio, there was an increase in the rate of ALSFRS-R decline per month associated with increases in tau levels. This decline was also inversely correlated with increases in pTau-T181 in relation to tau levels. Taken together, our findings demonstrate that, like Alzheimer’s disease, hyperphosphorylated tau is mis-localized in ALS and that decreases in CSF pTau-T181 may serve as a biomarker in ALS.
Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data
Authors: Volz Erik , Mishra Swapnil , Chand Meera , Barrett Jeffrey C. , Johnson Robert , Geidelberg Lily , Hinsley Wes R , Laydon Daniel J , Dabrera Gavin , O’Toole Áine , Amato Roberto , Ragonnet-Cronin Manon , Harrison Ian , Jackson Ben , Ariani Cristina V. , Boyd Olivia , Loman Nicholas J , McCrone John T , Gonçalves Sónia , Jorgensen David , Myers Richard , Hill Verity , Jackson David K. , Gaythorpe Katy , Groves Natalie , Sillitoe John , Kwiatkowski Dominic P. ,   The COVID-19 Genomics UK (COG-UK) consortium, Flaxman Seth , Ratmann Oliver , Bhatt Samir , Hopkins Susan , Gandy Axel , Rambaut Andrew , Ferguson Neil M 
Published: January 2021

AbstractThe SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.
Development of Electrospun Nanofibrous Filters for Controlling Coronavirus Aerosols
Authors: Wang Haihuan , Shen Hongchen , Zhou Zhe , Zhang Mengyang , Han Minghao , Durkin David P. , Shuai Danmeng , Shen Yun 
Published: January 2021

AbstractAirborne transmission of SARS-CoV-2 plays a critical role in spreading COVID-19. To protect public health, we designed and fabricated electrospun nanofibrous air filters that hold promise for applications in personal protective equipment and indoor environment. Due to ultrafine nanofibers (∼300 nm), the electrospun air filters had a much smaller pore size compared to the surgical mask and cloth masks (a couple of microns versus tens to hundreds of microns). A coronavirus strain was used to generate aerosols for filtration efficiency tests, which can better represent SARS-CoV-2 than other agents used for aerosol generation in previous studies. The electrospun air filters showed excellent performance by capturing up to 99.9% of coronavirus aerosols, which outperformed many commercial face masks. In addition, since NaCl aerosols have been widely used in filtration tests, we compared the filtration efficiency obtained from the coronavirus aerosols and the NaCl aerosols. The NaCl aerosols were demonstrated as an eligible surrogate for the coronavirus aerosols in the filtration tests, when air filters and face masks with diverse pore sizes, morphologies, and efficiencies were used. Our work paves a new avenue for advancing air filtration by developing electrospun nanofibrous air filters for controlling SARS-CoV-2 airborne transmission. Moreover, the removal efficiency of the NaCl aerosols can be reasonably translated into understanding how air filters capture the coronavirus aerosols.
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Integrative Bioinformatics Analysis Identifies Noninvasive miRNA Biomarkers for Lung Cancer
Authors: Gao Andrew 
Published: January 2021

AbstractNon-small cell lung cancer (NSCLC), a subtype of lung cancer, affects millions of people. While chemotherapy and other treatments have improved, the 5 year survival rate of NSCLC patients is still only 21%. Early diagnosis is essential for increasing survival as treatments have higher effectiveness at earlier stages of NSCLC. Noninvasive blood-based liquid biopsy tests for NSCLC may be useful for diagnosis and prognosis. MicroRNA (miRNA) and messenger RNA present in blood can serve as biomarkers for such tests. The present study identified 13 miRNAs that are underexpressed in the tissue and blood of NSCLC patients using Gene Expression Omnibus data. Following Kaplan Meier analysis, miR-140-3p, miR-29c, and miR-199a were selected as candidate biomarkers and demonstrated statistically significant prognostic power. An ROC analysis of miR-140-3p expression between NSCLC patients and controls had an area under curve value of 0.85. Functional enrichment analysis of the miRNA target genes revealed several overrepresented pathways relevant to cancer. Eight target genes were hub genes of the protein protein interaction network and possessed significant prognostic power. A combination of IL6, SNAI1, and CDK6 achieved a hazard ratio of 1.4 with p < 0.001. These biomarkers are especially valuable because they can be identified in blood and reflect the tumor state. Since all miRNAs were underexpressed in both tissue and blood, detecting expression of a biomarker miRNA in blood provides information on its expression in tissue as well. These miRNAs may be useful biomarkers for NSCLC prognostic and diagnostic tests and should be further studied.
Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2
Authors: Trombetta Bianca A. , Kandigian Savannah E. , Kitchen Robert R. , Grauwet Korneel , Kivisäkk Webb Pia , Miller Glenn A. , Jennings Charles G. , Jain Sejal , Miller Samara , Kuo Yikai , Sweeney Thadryan , Gilboa Tal , Norman Maia , Simmons Daimon P. , Ramirez Christopher E. , Bedard Melissa , Fink Catherine , Ko Jina , De León Peralta Esmarline J. , Watts Gerald , Gomez-Rivas Emma , Davis Vannessa , Barilla Rocky , Wang Jianing , Cunin Pierre , Bates Samuel , Morrison-Smith Chevaun , Nicholson Benjamin , Wong Edmond , El-Mufti Leena , Kann Michael , Bolling Anna , Fortin Brooke , Ventresca Hayden , Zhou Wen , Pardo Santiago , Kwock Megan , Hazra Aditi , Cheng Leo , Ahmad Q. Rushdy , Toombs James A. , Larson Rebecca , Pleskow Haley , Luo Nell Meosky , Samaha Christina , Pandya Unnati M. , De Silva Pushpamali , Zhou Sally , Ganhadeiro Zakary , Yohannes Sara , Gay Rakiesha , Slavik Jacqueline , Mukerji Shibani S. , Jarolim Petr , Walt David R. , Carlyle Becky C. , Ritterhouse Lauren L. , Suliman Sara 
Published: January 2021

AbstractBackgroundCOVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed.MethodsWe evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays’ performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10-40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence.ResultsCombined IgG+IgM sensitivities ranged from 33.9% to 94.6%, while combined specificities ranged from 92.6% to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%), and combined IgG+IgM sensitivity (94.6%). Furthermore, 11 LFAs and 8 LFAs showed perfect specificity for IgG and IgM, respectively, with 15 LFAs showing perfect combined IgG+IgM specificity. Lumiquick had the lowest estimated limit-of-detection (LOD) (0.1 μg/mL), followed by a similar LOD of 1.5 μg/mL for CareHealth, Cellex, KHB, and Vivachek.ConclusionWe provide a public resource of the accuracy of select lateral flow assays with potential for home testing. The cost-effectiveness, scalable manufacturing process, and suitability for self-testing makes LFAs an attractive option for monitoring disease prevalence and assessing vaccine responsiveness. Our web tool provides an easy-to-use interface to demonstrate the impact of prevalence and test accuracy on the positive predictive values.
Assessment of Polarized Piezoelectric SrBi4Ti4O15Nanoparticles as an alternative antibacterial agent
Authors: Swain Subhasmita , Rautray Tapash Ranjan 
Published: January 2021

AbstractStrontium bismuth titanate nanoparticles (SrBi4Ti4O15/SBT NPs,) and their polarized counterparts were prepared to assess their antibacterial efficacy on biomaterials. The structural properties of the SBT NPs were performed by X-ray diffraction and the antibacterial efficacy was evaluated againstStaphyllococcus aureus (S. aureus)pathogenic bacteria. Significant antibacterial activity of polarized SBT specimen was observed againstS. aureusbacteria. Results presented in this work confirmed that polarized SBT can effectively combat bacterial growth and prevent biofilm formation activity of pathogenic bacteria and hence they can be used as alternative antimicrobial agents.
The ancient cardioprotective mechanisms of ACE2 bestow SARS-CoV-2 with a wide host range
Authors: Castiglione Gianni M. , Zhou Lingli , Xu Zhenhua , Neiman Zachary , Hung Chien-Fu , Duh Elia J. 
Published: January 2021

AbstractSARS-CoV-2 infects a broader range of mammalian species than previously anticipated, suggesting there may be additional unknown hosts wherein the virus can evolve and potentially circumvent effective vaccines. We find that SARS-CoV-2 gains a wide host range by binding ACE2 sites essential for ACE2 carboxypeptidase activity. Six mutations found only in rodent species immune to SARS-CoV-2 are sufficient to abolish viral binding to human and dog ACE2. This is achieved through context-dependent mutational effects (intramolecular epistasis) conserved despite ACE2 sequence divergence between species. Across mammals, this epistasis generates sequence-function diversity, but through structures all bound by SARS-CoV-2. Mutational trajectories to the mouse conformation not bound by SARS-CoV-2 are blocked, by single mutations functionally deleterious in isolation, but compensatory in combination, explaining why human polymorphisms at these sites are virtually non-existent. Closed to humans, this path was opened to rodents via permissive cardiovascular phenotypes and ancient increases to ACE2 activity, serendipitously granting SARS-CoV-2 immunity. This reveals how ancient evolutionary trajectories are linked with unprecedented phenotypes such as COVID-19 and suggests extreme caution should be taken to monitor and prevent emerging animal reservoirs of SARS-CoV-2.One sentence summaryA conserved mechanism essential for ACE2 catalytic activity is exploited by SARS-CoV-2 binding, allowing the virus to infect a wide range of species.
High rates of diabetes and pre-diabetes in postpartum period in Indian GDM women
Authors: Chittaranjan S Yajnik , Sonali S Wagle , Sharvari R Shukla , Shailaja D Kale , Rasika S Ladkat , Himangi G Lubree , Dattatray S Bhat , Nilam S Memane , Phatak Sanat , Meenakumari K 
Published: January 2021

AbstractAimTo investigate postpartum glucose intolerance in South Asian Indian GDM women within 1 year of delivery.MethodsBetween 2001-2005, 220 women were treated for GDM at the Diabetes Unit, King Edward Memorial Hospital, Pune. GDM was diagnosed by 75g OGTT [WHO 1999 pregnancy criteria]. OGTT was repeated 3 months to 1 year postpartum. One hundred and nineteen non-GDM women were also studied.ResultsOf 220 GDM women [30years, BMI 26.0kg/m2] 9 women continued to be diabetic after delivery and a further 111 attended OGTT within one year of delivery. Two had IFG, 16 IGT and 23 diabetes [WHO 1999], thus 50[42%] women were glucose intolerant. Of the non-GDM, 1 had IFG, 8 IGT and 3 diabetes (10% glucose intolerant). Those who were hyperglycemic at follow up had stronger family history of diabetes [64% vs. 58%], were shorter [154.6 vs. 156.5cm], had higher FPG concentrations during pregnancy [5.27 vs. 4.99 mmol/L], and higher BMI [26.3 vs.25.0kg/m2] and waist circumference [88.0 vs. 82.3cm] at follow up compared to normoglycemic women. Hyperglycemia was not associated with GAD antibody positivity (4 vs 3 in normoglycemic).ConclusionWe describe one of the highest rates of postpartum hyperglycemia within a short time after delivery in young urban GDM women from India. Majority of risk factors for GDM were present from before pregnancy, and we propose that metabolic disturbances were also likely present. This has implications for peri-conceptional epigenetic programming of diabetes in the offspring. Pre-pregnancy screening and treatment of glucose intolerance and its risk factors in the high-risk populations could be an important measure for primordial prevention of diabetes.Key messagesWe describe one of the highest rates of postpartum hyperglycemia in young urban GDM women from India within a short time after delivery.Our results invite further research and policy discussion for screening and treatment of glucose intolerance before pregnancy in high-risk populations.
Directed brain connectivity identifies widespread functional network changes in Parkinson’s disease
Authors: Mijalkov Mite , Volpe Giovanni , Pereira Joana B. 
Published: January 2021

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by topological changes in large-scale functional brain networks. These networks are commonly analysed using undirected correlations between the activation signals of brain regions. However, this approach suffers from an important drawback: it assumes that brain regions get activated at the same time, despite previous evidence showing that brain activation features causality, with signals being typically generated in one region and then propagated to other ones. Thus, in order to address this limitation, in this study we developed a new method to assess whole-brain directed functional connectivity in patients with PD and healthy controls using anti-symmetric delayed correlations, which capture better this underlying causality. To test the potential of this new method, we compared it to standard connectivity analyses based on undirected correlations. Our results show that whole-brain directed connectivity identifies widespread changes in the functional networks of PD patients compared to controls, in contrast to undirected methods. These changes are characterized by increased global efficiency, clustering and transitivity as well as lower modularity. In addition, changes in the directed connectivity patterns in the precuneus, thalamus and superior frontal gyrus were associated with motor, executive and memory deficits in PD patients. Altogether, these findings suggest that directional brain connectivity is more sensitive to functional network changes occurring in PD compared to standard methods. This opens new opportunities for the analysis of brain connectivity and the development of new brain connectivity markers to track PD progression.
Past, present and future of the Spanish labour market: when the pandemic meets the megatrends
Authors: Dolado Juan J. , Felgueroso Florentino , Jimeno Juan F. 
Published: January 2021

Purpose
This paper aims to review the experience so far of the Spanish labour market during the Covid-19 crisis in the light of the existing institutions, its performance during past recessions and the policy measures adopted during the pandemic. Emphasis is placed on the role of worldwide trends in labour markets because of automation and artificial intelligence, in shaping a potential recovery of this (hopefully) transitory shock through a big reallocation process of employment and economic activity. It also highlights some innovations to employment and social policies needed to smooth the reallocation process and lessen the rise in inequality associated to technological trends.

Design/methodology/approach
Theory and empirics.

Findings
The Spanish labour market will subject to a great reallocation shock as a result of Covid-19 and secular technological changes. Reforms need to be undertaken.

Originality/value
An overview and some new results.
Next time, with empathy: revisiting the studio pedagogy for transitional housing for refugees
Authors: Swaranjali Pallavi , Patel Tina , Espersen-Peters Kurt 
Published: January 2021

PurposeShowing empathy can be, at best, a tricky prospect; teaching empathy is downright daunting. The authors taught an interior design studio project that designed hypothetical transitional housing for refugees coming to Canada. As the project evolved, it became imperative that students needed to address tangible issues experienced by the refugee client, namely trauma, rootlessness and marginalization and authentically empathize with their client. Hence, instructors needed to accurately structure and facilitate this engagement. The purpose of this paper is to present a summary of the evolution of this studio project as a case study, the revision of the project's pedagogical goals and establishing a new set of design parameters that engage the “self” and the “other” through alternate modes of thinking and reasoning.Design/methodology/approachThe paper is centered on a reflective case study of the studio project and the student's work. The results of the reflection are contextualized within pedagogical framework that emphasize alternate forms of teaching and learning that promotes authentic empathetic engagement.FindingsThe summary of these reflections arises from organically questioning the nature of traditional design studio pedagogy. It proposes divergent approaches, such as “abductive reasoning”, posing the project as a “wicked problem” to encourages lateral explorations and connections.Originality/valueThis paper questions the value of prescriptive design process and guides student learning by providing an experimental toolkit that encourages alternative exploration, research and thinking.