bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity in uninfected and previously infected individuals
Authors: Lucas Carolina , Vogels Chantal B. F. , Yildirim Inci , Rothman Jessica E. , Lu Peiwen , Monteiro Valter , Gelhausen Jeff R. , Campbell Melissa , Silva Julio , Tabachikova Alexandra , Muenker M. Catherine , Breban Mallery I. , Fauver Joseph R. , Mohanty Subhasis , Huang Jiefang ,   Yale SARS-CoV-2 Genomic Surveillance Initiative, Pearson Claire , Muyombwe Anthony , Downing Randy , Razeq Jafar , Petrone Mary , Ott Isabel , Watkins Anne , Kalinich Chaney , Alpert Tara , Brito Anderson , Earnest Rebecca , Murphy Steven , Neal Caleb , Laszlo Eva , Altajar Ahmad , Tikhonova Irina , Castaldi Christopher , Mane Shrikant , Bilguvar Kaya , Kerantzas Nicholas , Ferguson David , Schulz Wade , Landry Marie , Peaper David , Shaw Albert C. , Ko Albert I. , Omer Saad B. , Grubaugh Nathan D. , Iwasaki Akiko 
Published: July 2021

AbstractThe emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1–6. We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained higher antibody titers than uninfected individuals post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain than previously infected individuals 7 days after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination in the time-points analysed. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2) or with E484K (without N501Y/T). While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity.
Noninvasive optical monitoring of cerebral blood flow and EEG Spectral responses after Severe Traumatic Brain Injury: A Case Report
Authors: Poon Chien-Sing , Rinehart Benjamin , Langri Dharminder S. , Rambo Timothy M. , Miller Aaron J. , Foreman Brandon , Sunar Ulas 
Published: July 2021

ABSTRACTSurvivors of severe brain injury may require care in a neurointensive care unit (neuro-ICU), where the brain is vulnerable to secondary brain injury. Thus, there is a need for noninvasive, bedside, continuous cerebral blood flow monitoring approaches in the neuro-ICU. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data about brain activity and function. The present case demonstrates in a patient with traumatic brain injury, noninvasive cerebral blood flow transients can be recorded that correlate with gold-standard invasive measurements and with the frequency content changes in the EEG data during clinical care.
Validation of a Novel Molecular Assay to the Diagnostic of COVID-19 Based on Real Time PCR with High Resolution Melting
Authors: Ferreira Beatriz Iandra da Silva , Gomes Natália Lins da Silva , Coelho Wagner Luis da Costa Nunes Pimentel , Costa Vanessa Duarte da , Carneiro Vanessa Cristine de Souza , Kader Rafael Lopes , Amaro Marisa Pimentel , Villar Lívia Melo , Miyajima Fábio , Alves-Leon Soniza Vieira , de Paula Vanessa Salete , Leon Luciane Almeida Amado , Moreira Otacilio Cruz 
Published: July 2021

ABSTRACTWith the emergence of the Covid-19 pandemic, the world faced an unprecedented need for RT-qPCR-based molecular diagnostic tests, leading to a lack of kits and inputs, especially in developing countries. Hence, the costs for commercial kits and inputs were overrated, stimulating the development of alternative methods to detect SARS-CoV-2 in clinical specimens. The availability of the complete SARS-CoV-2 genome at the beginning of the pandemic facilitated the development of specific primers and standardized laboratory protocols for Covid-19 molecular diagnostic. High-sensitive and cost-effective molecular biology technique based on the Melting Temperature differences between purine and pyrimidine bases can be used to the detection and genotyping of pathogens in clinical specimens. Here, a RT-qPCR assays with High Resolution Melting (HRM-RTqPCR) was developed for different regions of the SARS-CoV-2 genome (RdRp, E and N) and an internal control (human RNAse P gene). The assays were validated using synthetic sequences from the viral genome and clinical specimens (nasopharyngeal swabs, serum and saliva) of sixty-five patients with severe or moderate COVID-19 from different states in Brazil, in comparison to a commercial TaqMan RT-qPCR assay, as gold standard. The sensitivity of the HRM-RTqPCR assays targeting N, RdRp and E were 94.12, 98.04 and 92.16%, with 100% specificity to the 3 targets, and diagnostic accuracy of 95.38, 98.46 and 93.85%, respectively. Thus, the HRM-RTqPCR emerges as an alternative and low-cost methodology to increase the molecular diagnostic of patients suspicious for Covid-19, especially in restricted-budget laboratories.
Comparison of kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222
Authors: Jayathilaka Deshni , Jeewandara Chandima , Gomes Laksiri , Jayadas Tibutius Thanesh Pramanayagam , Kamaladasa Achala , Guruge Dinuka , Darshana Pradeep , Ranasinghe Thushali , Abyrathna Inoka Sepali , Danasekara Saubhagya , Gunathilaka Buddini , Kuruppu Heshan , Wijewickrama Ananda , Wijayamuni Ruwan , Schimanski Lisa , Tan T.K. , Ogg Graham S. , Townsend Alain , Malavige Gathsaurie Neelika 
Published: July 2021

AbstractBackgroundWhile there have been many studies characterizing the IgG and IgA responses to different SARS-CoV-2 proteins in individuals with natural infection, the induction of IgG and IgA to different viral proteins in vaccinees have not been extensively studied. Therefore, we sought to investigate the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD2221, in Sri Lankan individuals.MethodsUsing Luminex assays, we characterized the IgG and IgA responses in patients with varying severity of illness and following a single dose of the vaccine at 4 weeks and 12 weeks since onset of illness or following vaccination. Haemagglutination test (HAT) was used to assess the antibodies to the receptor binding domain of SARS-CoV-2 wild type (WT), B.1.1.7, B.1.351 and B.1.617.2 (VOCs) and surrogate neutralizing test to measure ACE2 receptor blocking antibodies.ResultsThose with mild illness and in vaccinees, the IgG responses to S1, S2, RBD and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. Those who had a febrile illness in 2017 and 2018 (controls) also gave IgG and IgA high responses to the S2 subunit. In the vaccinees, the most significant rise was seen for the IgG antibodies to the S2 subunit (p<0.0001). Vaccinees had several fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with mild and moderate/severe illness at 4 weeks and 12 weeks. At 12 weeks the HAT titres were significantly lower to the B.1.1.7 in vaccinees and significantly lower in those with mild illness, and in vaccinees to B.1.351 and for B.1.617.2. No such difference was seen in those with moderate/severe illness.ConclusionsVaccinees had significantly less IgA to SARS-CoV-2, but comparable IgG responses to those with natural infection. However, following a single dose, vaccinees had reduced antibody levels to the variants of concern (VOC), which further declined with time, compared to natural infection.
The DiSCover Project: Protocol and Baseline Characteristics of a Decentralized Digital Study Assessing Chronic Pain Outcomes and Behavioral Data
Authors: Lee Jennifer L. , Cerrada Christian J. , Ying Vang Mai Ka , Scherer Kelly , Tai Caroline , Tran Jennifer L.A. , Juusola Jessie L. , Sang Christine N. 
Published: July 2021

AbstractBackgroundChronic pain affects approximately 50 million adults in the United States and impacts mood, everyday functioning, and quality of life. The challenges of analgesic clinical trials and, therefore, the approval of new non-opioid analgesics, are based in part on a fundamental lack of understanding of those outcomes that are relevant to an individual’s overall functioning.ObjectivesTo determine the behaviors and health outcomes associated with chronic pain. This manuscript presents an overview of the study design, baseline health and behavioral characteristics of our sample, and preliminary findings of how behavioral characteristics differ between individuals with and without chronic pain.MethodsThe study is a decentralized digital longitudinal cohort study of 10,036 individuals (5,832 with chronic pain [CP] and 4,204 with no chronic pain [NCP]), age 18 years or older, living in the United States. The study period was one year. Data were collected from wearable activity trackers and health or fitness mobile applications to capture passively collected behavioral data including steps, sleep, and heart rate. Patient-reported outcomes on mood and pain, including the BPI-SF, PHQ-9, and GAD-7, were collected at various timepoints during the study.ResultsThe data suggest greater levels of depression and anxiety, lower quality of life, less physical activity, more variable sleep, and higher resting heart rate are associated with CP.ConclusionsThe longitudinal data from the larger study will yield substantial contributions to the body of literature in chronic pain, particularly in delineating relational and causal factors relevant to the impact of chronic pain, and potential development of a digital biomarker to assess and monitor patients’ everyday experience with chronic pain.
A Poisson binomial based statistical testing framework for comprehensive comorbidity discovery across massive Electronic Health Record datasets
Authors: Lemmon Gordon , Wesolowski Sergiusz , Henrie Alex , Tristani-Firouzi Martin , Yandell Mark 
Published: July 2021

AbstractDiscovery of comorbidities (the concomitant occurrence of distinct medical conditions in the same patient) is a prerequisite for creating forecasting tools for downstream outcomes research. Current comorbidity discovery applications are designed for small datasets and use stratification to control for confounding variables such as age, sex, or ancestry. Stratification lowers false positive rates, but reduces power, as the size of the study cohort is decreased. Here, we describe a Poisson Binomial based approach to comorbidity discovery (PBC) designed for big-data applications that circumvents the need for stratification. PBC adjusts for confounding demographic variables on a per-patient basis, and models temporal relationships. We benchmark PBC using two datasets, the publicly available MIMIC-IV; and the entire Electronic Health Record (EHR) corpus of the University of Utah Hospital System, encompassing over 1.6 million patients, to compute comorbidity statistics on 4,623,841 pairs of potentially comorbid medical terms. The results of this computation are provided as a searchable web resource. Compared to current methods, the PBC approach reduces false positive associations, while retaining statistical power to discover true comorbidities.
Trans Cohorts Metabolomic Modulation Following Long-Term Successful Therapy in HIV-Infection
Authors: Mikaeloff Flora , Svensson-Akusjärvi Sara , Ikomey George Mondinde , Krishnan Shuba , Sperk Maike , Gupta Soham , Vega Magdaleno Gustavo Daniel , Escós Alejandra , Lyonga Emilia , Okomo Marie Claire , Tagne Claude Tayou , Babu Hemalatha , Lorson Christian L , Végvári Ákos , Banerjea Akhil C. , Kele Julianna , Hanna Luke Elizabeth , Singh Kamal , de Magalhães João Pedro , Benfeitas Rui , Neogi Ujjwal 
Published: July 2021

AbstractDespite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic adaptation in people living with HIV (PLWH). The successful short-term cART reported abnormalities in the metabolic reprogramming in PLWH, but the long-term consequences are unknown. This study investigated alterations in the plasma metabolic profiles by comparing PLWH and matched HIV-negative controls (HC) from Cameroon and India. We used untargeted and targeted LC-MS/MS-based metabolic profiling in PLWH with long-term (>5years) successful therapy in a trans cohorts’ approach. Advanced statistical and bioinformatics analyses showed altered amino acid metabolism, more specifically to glutaminolysis in PLWH with therapy than HIV-negative controls that can lead to excitotoxicity in both the cohorts. A significantly lower level of neurosteroids was observed in both cohorts and could potentiate neurological impairments in PLWH. The modulation of cellular glutaminolysis promoted increased cell death and latency reversal in pre-monocytic HIV-1 latent cell model U1, which may be essential for the clearance of the inducible reservoir in HIV-integrated cells. Our patient-based metabolomics andin vitrostudy, therefore, highlight the importance of altered glutaminolysis in PLWH that can be linked accelerated neurocognitive aging and metabolic reprogramming in latently infected cells.
Predicting Infectivity: Comparing Four PCR-based Assays to Detect Culturable SARS-CoV-2 in Clinical Samples
Authors: Bruce Emily A. , Mills Margaret G. , Sampoleo Reigran , Perchetti Garrett A. , Huang Meei-Li , Despres Hannah W. , Shirley David J. , Jerome Keith R. , Greninger Alexander L. , Botten Jason W. 
Published: July 2021

ABSTRACTWith the COVID-19 pandemic caused by SARS-CoV-2 now in its second year, there remains an urgent need for diagnostic testing that can identify infected individuals, particularly those who harbor infectious virus. Various RT-PCR strategies have been proposed to identify specific viral RNA species that may predict the presence of infectious virus, including detection of transcriptional intermediates (e.g. subgenomic RNA [sgRNA]) and replicative intermediates (e.g. negative-strand RNA species). Using a novel primer/probe set for detection of subgenomic (sg)E transcripts, we successfully identified 100% of specimens containing culturable SARS-CoV-2 from a set of 126 clinical samples (total sgE CT values ranging from 12.3-37.5). This assay showed superior performance compared to a previously published sgRNA assay and to a negative-strand RNA assay, both of which failed to detect target RNA in a subset of samples from which we isolated live virus. In addition, total levels of viral RNA (genome, negative-strand, and sgE) detected with the WHO/Charité primer-probe set correlated closely with levels of infectious virus. Specifically, infectious virus was not detected in samples with a CT above 31.0. Clinical samples with higher levels of viral RNA also displayed cytopathic effect (CPE) more quickly than those with lower levels of viral RNA. Finally, we found that the infectivity of SARS-CoV-2 samples is significantly dependent on the cell type used for viral isolation, as Vero E6 cells expressing TMRPSS2 extended the analytical sensitivity of isolation by more than 3 CT compared to parental Vero E6 cells and resulted in faster isolation. Our work shows that using a total viral RNA Ct cut-off of >31 or specifically testing for sgRNA can serve as an effective rule-out test for viral infectivity.
Cortical function and sensorimotor plasticity predict future low back pain after an acute episode: the UPWaRD prospective cohort study
Authors: Jenkins Luke C , Chang Wei-Ju , Buscemi Valentina , Liston Matthew , Humburg Peter , Nicholas Michael , Graven-Nielsen Thomas , Hodges Paul W , McAuley James H , Schabrun Siobhan M 
Published: July 2021

ABSTRACTPredicting the development of chronic low back pain (LBP) at the time of an acute episode remains challenging. The Understanding persistent Pain Where it ResiDes (UPWaRD) study aimed to identify neurobiological and psychological risk factors for chronic LBP. Individuals with acute LBP (N=120) participated in a prospective cohort study with six-month follow-up. Candidate predictors were selected from the neurobiological (e.g. sensorimotor cortical excitability assessed by sensory and motor evoked potentials, Brain Derived Neurotrophic Factor genotype), psychological (e.g. depression and anxiety), symptom-related (e.g. LBP history) and demographic domains. Analyses involved multivariable linear regression models with pain intensity or disability degree as continuous variables. Secondary analyses involved a multivariable logistic model with presence of low back pain at six months (thresholding pain intensity and disability degree) as a dichotomous variable. Lower sensory cortex and corticomotor excitability, higher baseline pain intensity, higher depression, stress and pain catastrophizing were the strongest predictors (R2=0.47) of pain intensity at six months. Older age and higher pain catastrophizing were the strongest predictors (R2=0.30) of disability at six months. When LBP outcome was dichotomised, sensory cortex and corticomotor excitability, BDNF genotype, depression and anxiety, LBP history and baseline pain intensity, accurately discriminated those who did and did not report LBP at six months (c-statistic 0.91). This study identifies novel risk factors for future LBP after an acute episode that can predict an individual’s pain intensity and level of disability at six-month follow-up, and accurately discriminate between those who will and will not report LBP at six months.
Potential applications of the rapid COVID-19 antibody test kit screening in comparison to the RT-PCR in patients and personnel at the Department of Obstetrics and Gynecology
Authors: Narkwichean Amarin , Jomoui Wittaya , Boonpradit Rarinthip , Laosooksathit Wipada , Nopsopon Tanawin , Pongpirul Krit 
Published: July 2021

AbstractObjectiveTo explore potential applications of the rapid antibody test for COVID-19 screening, in comparison to RT-PCR, for emergency obstetric and gynecological procedures, and medical personnel in the Department of Obstetrics and Gynecology.MethodsA cross-sectional study was conducted in expected 290 participants: 230 patients and 60 medical staff, during the four-month national COVID-19 outbreak period (Aug – Sep 2020, and Dec 2020 - Jan 2021). All participants underwent both rapid antibody tests and RT-PCR (at admission for patients).ResultsA total of 270 participants completed the study. Fever and URI symptoms were present in 6/210 patients (2.8%) while one patient (0.5%) had a history of traveling to a high-risk area. However, only two (1%) asymptomatic patients had positive IgM results. Concerning the medical personnel, 10% fell into the ‘patient under investigation (PUI)’ category. 4/60 (6.7%) IgM positive was observed in the staff cohort in which 3/4 came from non-PUI participants. Neither participant had RT-PCR positive demonstrating a 1.9% total false positive rate.ConclusionRapid point-of-care antibody test can be used to screen either a pregnant coming for delivery, a patient who requires urgent/emergency operative procedures, or medical personnel, at least in the defined lower-prevalence COVID-19 situation.Trial registrationThis study was approved by the Institutional Review Board of Srinakharinwirot University (IRB SWUEC119/2563F) and was registered at the Thai Clinical Trials Registry (TCTR20210613001).
Modelling infectious disease transmission potential as a function of human behaviour
Authors: Walters Caroline E. , Dunbar Maria Bekker-Nielsen , Weston Dale , Hall Ian M. 
Published: July 2021

AbstractMathematical modelling is an important public health tool for aiding understanding the spread of respiratory infectious diseases, such as influenza or COVID-19, and for quantifying the effects of behavioural interventions. However, such models rarely explicitly appeals to theories of human behaviour to justify model assumptions. Here we propose a novel mathematical model of disease transmission via fomites (luggage trays) at airport security screening during an outbreak. Our model incorporates the self-protective behaviour of using hand sanitiser gel in line with the extended parallel processing model (EPPM) of behaviour.We find that changing model assumptions of human behaviour in line with the EPPM gives qualitatively different results on the optimal placement of hand sanitiser gels within an airport compared to the model with naive behavioural assumptions. Specifically, that it is preferable to place hand sanitiser gels after luggage screening in most scenarios, however in situations where individuals perceive high threat and low efficacy this strategy may need to be reviewed. This model demonstrates how existing behavioural theories can be incorporated into mathematical models of infectious disease.
SARS-CoV-2 seroprevalence in Chattogram, Bangladesh before the Delta surge, March-June 2021
Authors: Bhuiyan Taufiqur Rahman , Dent Hulse Juan , Hegde Sonia T. , Akhtar Marjahan , Islam Md. Taufiqul , Hasan Khan Zahid , Khan Ishtiakul Islam , Ahmed Shakeel , Rashid Md Mamunur , Rashid Rumana , Gurley Emily S. , Shirin Tahmina , Khan Ashraful Islam , Azman Andrew S. , Qadri Firdausi 
Published: July 2021

AbstractIn a representative serosurvey conducted March–June 2021, 64.1% (95%CrI 60.0– 68.1%) of Sitakunda subdistrict (Bangladesh) had anti-SARS-CoV-2 IgG antibodies after adjusting for age, sex, household clustering and test performance. Before the surge of Delta, most of the population had been infected despite low incidence of virologically-confirmed COVID-19.
Tobacco and Nicotine Use in the United States Army Trainee Soldier’s Environment
Authors: Lang Adam Edward , Yakhkind Aleksandra , Prom-Wormley Elizabeth 
Published: July 2021

AbstractTobacco and nicotine use rates within the United States military population are high, and rates among young trainee soldiers are not improving over time. Trainee soldiers are heavily influenced by role models in their environment, and nicotine product use rates in this environment has not previously been evaluated. This study found that over 30% of non-trainee U.S. Army soldiers, known as cadre, within the training environment use nicotine products. For the young trainee soldier, this creates an initial Army experience that continues to foster a culture of tobacco and nicotine use. We urge changes in Army tobacco and nicotine policy to protect the vulnerable trainee soldier population.