bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutralising antibody activity against SARS-CoV-2 variants, including Omicron, in an elderly cohort vaccinated with BNT162b2
Authors: Newman Joseph , Thakur Nazia , Peacock Thomas P. , Bialy Dagmara , Elreafey Ahmed ME , Bogaardt Carlijn , Horton Daniel L. , Ho Sammy , Kankeyan Thivya , Carr Christine , Hoschler Katja , Barclay Wendy S. , Amirthalingam Gayatri , Brown Kevin , Charleston Bryan , Bailey Dalan 
Published: December 2021

AbstractSARS-CoV-2 variants threaten the effectiveness of tools we have developed to mitigate against serious COVID-19. This is especially true in clinically vulnerable sections of society including the elderly. Using sera from BNT162b2 (Pfizer–BioNTech) vaccinated individuals aged between 70 and 89 (vaccinated with two doses 3-weeks apart) we examined the neutralising antibody (nAb) response to wildtype SARS-CoV-2. Between 3 and 20-weeks post 2nddose, nAb titres dropped 4.9-fold to a median titre of 21.3 (ND80) with 21.6% of individuals having no detectable nAbs at the later time point. Experiments examining the neutralisation of twenty-one different SARS-CoV-2 variant spike proteins confirmed a significant potential for antigenic escape, especially for the Omicron (BA.1), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 variants. Interestingly, however, the recently-emerged sub-lineage AY.4.2 was more efficiently neutralised than parental Delta pseudotypes. Combining pseudotype neutralisation with specific receptor binding domain (RBD) ELISAs we confirmed that changes to position 484 in the spike RBD were predominantly responsible for SARS-CoV-2 nAb escape, although the effect of spike mutations is both combinatorial and additive. Lastly, using sera from the same individuals boosted with a 3rddose of BNT162b2 we showed that high overall levels of neutralising antibody titre can provide significant levels of cross-protection against Omicron. These data provide evidence that SARS-CoV-2 neutralising antibodies wane over time and that antigenically variable SARS-CoV-2 variants are circulating, highlighting the importance of ongoing surveillance and booster programmes. Furthermore, they provide important data to inform risk assessment of new SARS-CoV-2 variants, such as Omicron, as they emerge.
Three doses of the BNT162b2 vaccine confer neutralising antibody capacity against the SARS-CoV-2 B.1.1.529 (Omicron) variant of concern
Authors: Ariën Kevin K. , Heyndrickx Leo , Michiels Johan , Vereecken Katleen , Van Lent Kurt , Coppens Sandra , Pannus Pieter , Martens Geert A. , Van Esbroeck Marjan , Goossens Maria E. , Marchant Arnaud , Bartholomeeusen Koen , Desombere Isabelle 
Published: December 2021

AbstractWe report the levels of neutralising antibodies against Wuhan, Delta and Omicron variants in healthy individuals pre-infected or not with SARS-CoV-2 and immunized with three doses of the BNT162b2 vaccine. Our observations support the rapid administration of a booster vaccine dose to prevent infection and disease caused by Omicron.
Tracking community infection dynamics of COVID-19 by monitoring SARS-CoV-2 RNA in wastewater, counting positive reactions by qPCR
Authors: Zhao Bo , Yu Zaizhi , Fujita Tomonori , Nihei Yoshiaki , Tanaka Hiroaki , Ihara Masaru 
Published: December 2021

AbstractWastewater-based epidemiology has proved useful for monitoring the COVID-19 infection dynamics in communities. However, in some countries, low concentrations of SARS-CoV-2 RNA in wastewater make this difficult. Getting meaningful information from wastewater-based epidemiology in regions of low prevalence remains a key challenge. Here we used real-time reverse-transcription PCR (RT-qPCR) to monitor SARS-CoV-2 RNA in wastewater from October 2020 to February 2021 during the third wave of the COVID-19 outbreak in Japan. Viral RNA was below the limit of quantification in all samples. However, by counting the positive reactions in repeated qPCR of each sample, we found that the ratio of positive reactions to all tests in wastewater was significantly correlated with the number of clinically confirmed cases by the date of symptom onset during periods of both increasing and decreasing infection. Time-step analysis indicated that COVID-19 patients excreted large amounts of virus in their feces 2 days either side of symptom onset, which wastewater surveillance could detect. The positive count method is thus useful for tracing COVID-19 dynamics in regions of low prevalence.HighlightsPositive ratio by repeated qPCR of low target-molecule numbers correlated with number expected from Poisson distribution.Positive ratio by repeated RT-qPCR of SARS-CoV-2 RNA in wastewater tracked the infection dynamics of COVID-19 in a region of low prevalence.Positive ratios correlated with number of new cases by date of symptom onset.COVID-19 patients might excrete more virus in their feces in the period from 2 days before to 2 days after symptom onset.
Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19
Authors: Coelho dos Reis Jordana Grazziela A. , Ferreira Geovane Marques , Lourenço Alice Aparecida , Ribeiro Ágata Lopes , Martins da Mata Camila Pacheco da Silveira , de Melo Oliveira Patrícia , de Almeida Marques Daisymara Priscila , Ferreira Linziane Lopes , Clarindo Felipe Alves , da Silva Murillo Ferreira , Póvoas Filho Heitor Portella , Oliveira Junior Nilson Roberto Ribeiro , D’Carmo Sodré Maisah Meyhr , Gadelha Sandra Rocha , Albuquerque George Rego , Maciel Bianca Mendes , Melo Mariano Ana Paula , de Melo Silva Mylene , Fontana Renato , Marin Lauro Juliano , Alberto Carlos Renata Santiago , Sampaio Lopes Amanda Teixeira , Ferreira Fabrício Barbosa , dos Santos Uener Ribeiro , de Santana Íris Terezinha Santos , Fehlberg Hllytchaikra Ferraz , Rezende Rachel Passos , Dias João Carlos T , Gross Eduardo , Castro Goulart Gisele Assis , Santiago Marie Gabriele , de Lemos Ana Paula Motta Lavigne , da Conceição Aline O , Romano Carla Cristina , de Carvalho Luciana Debortoli , Martins Filho Olindo Assis , Quadros Claudio Almeida , Valle Sarah J , Morris David L 
Published: December 2021

AbstractCOVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic, antiviral, and anti-inflammatory effect of BromAc®in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation.MethodTracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine storm analysis was performed.ResultsBromAc®displayed a robust mucolytic effect in a dose dependent manner. BromAc®showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1RA and total reduction for IL-9 compared to NAC alone and control. BromAc®acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250µg.ConclusionThese results indicate robust mucolytic and anti-inflammatory effect of BromAc®in tracheal aspirates from critically ill COVID-19 patients, indicating its potential as a therapeutic strategy to COVID-19.
Analysis of anti-Omicron neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources
Authors: Sullivan David J , Franchini Massimo , Joyner Michael J. , Casadevall Arturo , Focosi Daniele 
Published: December 2021

AbstractThe latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates the continued relevance of COVID- 19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on early outpatients and immunocompromised recipients, with high neutralizing antibody (nAb) titer units. In this analysis we systematically reviewed Omicron-neutralizing plasma activity data, and found that approximately 47% (424/902) of CCP from unvaccinated pre-Omicron donors neutralizes Omicron BA.1 with a very low geomean of geometric mean titers for 50% neutralization GM(GMT50) of about 13, representing a more than 20-fold reduction from WA-1 neutralization. Two doses of mRNA vaccines in nonconvalescent subjects had a similar 50% percent neutralization with Omicron BA.1 neutralization GM(GMT(50)) of about 27. However, plasma from vaccinees recovered from either previous pre-Omicron variants of concern infection, Omicron BA.1 infection, or third-dose uninfected vaccinees was nearly 100% neutralizing against Omicron BA.1, BA.2 and BA.4/5 with GM(GMT(50)) all over 189, 10 times higher than pre-Omicron CCP. Fully vaccinated and post-BA.1 plasma (Vax-CCP) had GM(GMT50) over 450 for BA.4/5 and over 1500 for BA.1 and BA.2. These findings have implications for both CCP stocks collected in prior pandemic periods and plans to restart CCP collections. Thus, Vax-CCP provides an effective tool to combat ongoing variants that defeat therapeutic monoclonal antibodies.
A novel methodology for the synchronous collection and multimodal visualisation of continuous neurocardiovascular and neuromuscular physiological data in adults with long COVID
Authors: Xue Feng , Monaghan Ann , Jennings Glenn , Byrne Lisa , Foran Tim , Duggan Eoin , Romero-Ortuno Roman 
Published: December 2021

AbstractReports suggest that adults with post-COVID-19 syndrome or long COVID may be affected by orthostatic intolerance syndromes, with autonomic nervous system dysfunction as a possible causal factor of neurocardiovascular instability (NCVI). Long COVID can also manifest as prolonged fatigue, which may be linked to neuromuscular function impairment (NMFI). The current clinical assessment for NCVI monitors neurocardiovascular performance upon the application of orthostatic stressors such as an active (i.e. self-induced) stand or a passive (tilt table) standing test. Lower limb muscle contractions may be important in orthostatic recovery via the skeletal muscle pump. In this study, adults with long COVID were assessed with a protocol that, in addition to the standard NCVI tests, incorporated simultaneous lower limb muscle monitoring for NMFI assessment. To accomplish such an investigation, a wide range of continuous non-invasive biomedical technologies were employed, including digital artery photoplethysmography for the extraction of cardiovascular signals, near-infrared spectroscopy for the extraction of regional tissue oxygenation in brain and muscle, and electromyography for assessment of timed muscle contractions in the lower limbs. With the novel technique described and exemplified in this paper, we were able to integrate signals from all instruments used in the assessment in a precisely synchronized fashion. We demonstrate that it is possible to visualize the interactions between all different physiological signals during the combined NCVI/NMFI assessment. Multiple counts of evidence were collected, which can capture the dynamics between skeletal muscle contractions and neurocardiovascular responses. The proposed multimodal data visualization can offer an overview of the functioning of the muscle pump during both supine rest and orthostatic recovery and can conduct comparison studies with signals from multiple participants at any given time in the assessment. This could help researchers and clinicians generate and test hypotheses based on the multimodal inspection of raw data, in long COVID and other clinical cohorts.
Healthcare workers’ COVID-19 Omicron variant uncertainty-related stress, resilience, and coping strategies during the first week of World Health Organization alert
Authors: Temsah Mohamad-Hani , Alenezi Shuliweeh , Al-Arabi Mohamad , Aljamaan Fadi , Alhasan Khalid , Assiri Rasha , Bassrawi Rolan , Alshahrani Fatimah , Alhaboob Ali , Alaraj Ali , Alharbi Naser S , Halwani Rabih , Jamal Amr , Abdulmajeed Naif , Alfarra Lina , Almashdali Wafa , Al-Eyadhy Ayman , AlZamil Fahad , Al-Subaie Sarah , Barry Mazin , Memish Ziad A. , Al-Tawfiq Jaffar A. 
Published: December 2021

AbstractBackgroundAs the COVID-19 Omicron variant emerged and spread globally at an alarming speed, healthcare workers’ (HCWs) uncertainties, worries, resilience, and coping strategies warrant assessment. The COVID-19 pandemic had a severe psychological impact on HCWs, including the development of Post-Traumatic Stress symptoms. Specific subgroups of HCWs, such as front-line and female workers, were more prone to poor mental health outcomes and difficulties facing stress.MethodsThe responses to an online questionnaire among HCWs in Saudi Arabia (KSA) were collected December 1-5, 2021, aiming to assess their Omicron variant’s uncertainties, worries, resilience, and coping strategies. Three validated instruments were used to achieve the study’s goals: the Brief Resilient Coping Scale, the Standard Stress Scale (SSS), and the Intolerance of Uncertainty Scale (IUS) - Short Form.ResultsThe online survey was completed by 1285 HCWs. Females made up the majority (64%). The BRCS score of resilient coping was negatively and substantially linked with the SSS score of stress (r=-0.313, p = 0.010). Furthermore, the IUS had a positive and significant relationship with stress (r=0.326, p= 0.010). Increased stress levels were linked to a considerable drop in resilient coping scores. Furthermore, being a Saudi HCW or a nurse was linked to a significant reduction in resilient coping ratings. Coping by following healthcare authorities’ preventative instructions and using the WHO website as a source of information was linked to a considerable rise in resilient coping.ConclusionsFollowing the emergence of the Omicron variant of SARS-CoV-2 in late 2021, a rapid investigation into the correlates of stress and resilient coping among the HCWs in KSA was conducted. The negative association between resilient coping and stress was clearly shown, as well as how underlying intolerance of uncertainty is linked to higher stress among HCWs quickly following the development of a new infectious threat. The study provides early insights to develop and promote coping strategies for emerging SARS-CoV-2 variants.
Multi-omics and 3D-imaging reveal bone heterogeneity and unique calvaria cells in neuroinflammation
Authors: Kolabas Zeynep Ilgin , Kuemmerle Louis B. , Perneczky Robert , Förstera Benjamin , Büttner Maren , Caliskan Ozum Sehnaz , Ali Mayar , Rong Zhouyi , Mai Hongcheng , Hummel Selina , Bartos Laura M. , Biechele Gloria , Zatcepin Artem , Albert Natalie L. , Unterrainer Marcus , Gnörich Johannes , Zhao Shan , Khalin Igor , Rauchmann Boris-Stephan , Molbay Muge , Sterr Michael , Kunze Ines , Stanic Karen , Besson-Girard Simon , Kopczak Anna , Katzdobler Sabrina , Palleis Carla , Gokce Ozgun , Lickert Heiko , Steinke Hanno , Bechmann Ingo , Buerger Katharina , Levin Johannes , Haass Christian , Dichgans Martin , Havla Joachim , Kümpfel Tania , Kerschensteiner Martin , Simons Mikael , Plesnila Nikolaus , Krahmer Natalie , Bhatia Harsharan Singh , Erener Suheda , Hellal Farida , Brendel Matthias , Theis Fabian J. , Erturk Ali 
Published: December 2021

SUMMARYThe meninges of the brain are an important component of neuroinflammatory response. Diverse immune cells move from the calvaria marrow into the dura mater via recently discovered skull-meninges connections (SMCs). However, how the calvaria bone marrow is different from the other bones and whether and how it contributes to human diseases remain unknown. Using multi-omics approaches and whole mouse transparency we reveal that bone marrow cells are highly heterogeneous across the mouse body. The calvaria harbors the most distinct molecular signature with hundreds of differentially expressed genes and proteins. Acute brain injury induces skull-specific alterations including increased calvaria cell numbers. Moreover, TSPO-positron-emission-tomography imaging of stroke, multiple sclerosis and neurodegenerative disease patients demonstrate disease-associated uptake patterns in the human skull, mirroring the underlying brain inflammation. Our study indicates that the calvaria is more than a physical barrier, and its immune cells may present new ways to control brain pathologies.Graphical AbstractHighlightsBone marrow across the mouse body display heterogeneity in their molecular profileCalvaria cells have a distinct profile that is relevant to brain pathologiesBrain native proteins are identified in calvaria in pathological statesTSPO-PET imaging of the human skull can be a proxy of neuroinflammation in the brainSupplementary Videos can be seen at: http://discotechnologies.org/Calvaria/
eIF4A2 targets developmental potency and histone H3.3 transcripts for translational control of stem cell pluripotency
Authors: Li Dan , Yang Jihong , Huang Xin , Zhou Hongwei , Wang Jianlong 
Published: December 2021

AbstractTranslational control has emerged as a fundamental regulatory layer of proteome complexity that governs cellular identity and functions. As initiation is the rate-limiting step of translation, we carried out an RNAi screen for key translation initiation factors required to maintain embryonic stem cell (ESC) identity. We identified eIF4A2 and defined its mechanistic action through Rps26-independent and -dependent ribosomes in translation initiation activation of mRNAs encoding pluripotency factors and the histone variant H3.3 with demonstrated roles in maintaining stem cell pluripotency. eIF4A2 also mediates translation initiation activation of Ddx6, which acts together with eIF4A2 to restrict the totipotent 2-cell transcription program in ESCs through Zscan4 mRNA degradation and translation repression. Accordingly, knockdown of eIF4A2 disrupts ESC proteome causing the loss of ESC identity. Collectively, we establish a translational paradigm of the protein synthesis of pluripotency transcription factors and epigenetic regulators imposed on their established roles in controlling pluripotency.
Optogenetic frequency scrambling of hippocampal theta oscillations dissociates working memory retrieval from hippocampal spatiotemporal codes
Authors: Etter Guillaume , van der Veldt Suzanne , Choi Jisoo , Williams Sylvain 
Published: December 2021

AbstractThe precise temporal coordination of activity in the brain is thought to be fundamental for memory encoding and retrieval. Pacemaker GABAergic neurons in the medial septum (MS) provide the largest source of innervation to the hippocampus and play a major role in controlling hippocampal theta (~8 Hz) oscillations. While pharmacological inhibition of the MS is known to disrupt memory, the exact role of MS inhibitory neurons and theta frequency rhythms in hippocampal representations and memory is not fully understood. Here, we dissociate the role of theta rhythms in spatiotemporal coding and memory using an all-optical interrogation and recording approach in freely behaving mice. We propose a novel paradigm to dissociate encoding of space, time and distance in freely moving mice and apply complementary optogenetic stimulation paradigms of MS GABAergic neurons to either pace or abolish theta altogether while recording large hippocampal cell assemblies using calcium imaging conjointly. We first show that optogenetic frequency scrambling of MS GABAergic neuron activity abolished theta rhythms and modulated the activity of a subpopulation of CA1 neurons. Such stimulation led to decreased memory retrieval in both a delayed non-match to sample task, a novel place object recognition task, as well as spontaneous cue-guided linear alternation. Strikingly, scrambled stimulations were not associated with disrupted encoding of place, time, distance, or multiplexed information. Our study suggests that theta rhythms play a specific and essential role in supporting working memory retrieval and maintenance while not being necessary for hippocampal spatiotemporal codes.
Improved immunoassay sensitivity and specificity using single-molecule colocalization
Authors: Hariri Amani A. , Newman Sharon S. , Tan Steven , Mamerow Dan , Eisenstein Michael , Dunn Alexander , Soh H. Tom 
Published: December 2021

AbstractEnzyme-linked immunosorbent assays (ELISAs) are a cornerstone of modern molecular detection, but the technique still suffers some notable challenges. One of the biggest problems is discriminating true signal generated by target molecules versus non-specific background arising from the interaction of detection antibodies with the assay substrate or interferents in the sample matrix. Single-Molecule Colocalization Assay (SiMCA) overcomes this problem by employing total internal reflection fluorescence (TIRF) microscopy to quantify target proteins based on the colocalization of fluorescent signal from orthogonally labeled capture and detection antibodies. By specifically counting colocalized fluorescent signals, we can essentially eliminate the confounding effects of background produced by non-specific binding of detection antibodies. We further employed a normalization strategy to account for the heterogeneous distribution of the capture antibodies, greatly improving the reproducibility of our measurements. In a series of experiments with TNF-α, we show that SiMCA can achieve a three-fold lower limit of detection compared to conventional single-color assays using the same antibodies and exhibits consistent performance for assays performed in complex specimens such as chicken serum and human blood. Our results help define the pernicious effects of non-specific background in immunoassays and demonstrate the diagnostic gains that can be achieved by eliminating those effects.
Enhancing turbulence: a potential strategy for drag reduction based on ground transportation systems (GTS) model
Authors: Yang Xiaolong , Liu Zhuangzhi , Hu Yu 
Published: December 2021

Purpose
The purpose of this paper is to investigate the mechanism and performance of a potential strategy, which is to enhance turbulence to carry out drag reduction for heavy trucks.

Design/methodology/approach
Enhancing turbulence deflector (ETD) was placed on the roof surface of an ground transportation system (GTS) to investigate the drag reduction mechanism of enhancing turbulence. Transition shear-stress transport improved delay detach eddy simulation model was adopted to simulate the unsteady small-scale flow around the ETD.

Findings
By optimizing the three influencing factors, diameter, streamwise length and streamwise position, the optimized ETD has achieved a maximum drag reduction of 7.04%. The analysis of flow field results shows that enhancing turbulence can effectively suppress flow separation and reduce the negative pressure intensity in the wake region of GTS.

Originality/value
The present work provides another potential possibility for the improvement of the aerodynamic performance of heavy trucks.