bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical and clinical validation of a novel injected molded swab for molecular assay detection of SARS-CoV-2 virus
Authors: Ghezzi Chiara E. , Hartigan Devon R. , Hardick Justin , Gore Rebecca , Adelfio Miryam , Diaz Anyelo R. , McGuinness Pamela D. , Robinson Matthew L. , Buchholz Bryan O. , Manabe Yukari C. 
Published: October 2021

AbstractDuring the COVID-19 public health emergency, many actions have been undertaken to help ensure that patients and health care providers had timely and continued access to high-quality medical devices to respond effectively. The development and validation of new testing supplies and equipment, including collection swab, help expand the availability and capability for various diagnostic, therapeutic, and protective medical devices in high demand during the COVID-19 emergency. Here, we report the validation of a new injection-molded anterior nasal swab, ClearTip™, that was experimentally validated in a laboratory setting as well as in independent clinical studies in comparison to gold standard flocked swabs. We have also developed an in vitro anterior nasal tissue model, that offers an efficient and clinically relevant validation tool to replicate with high fidelity the clinical swabbing workflow, while being accessible, safe, reproducible, time and cost effective. ClearTip™ displayed a greater efficiency of release of inactivated virus in the benchtop model, confirmed by greater ability to report positive samples in a clinical study in comparison to flocked swabs. We also quantified in multi-center pre-clinical and clinical studies the detection of biological materials, as proxy for viral material, that showed a statistically significant difference in one study and a slight reduction in performance in comparison to flocked swabs. Taken together these results underscore the compelling benefits of non-absorbent injected molded anterior nasal swab for COVID-19 detection, comparable to standard flocked swabs. Injection-molded swabs, as ClearTip™, could have the potential to support future swab shortage, due to its manufacturing advantages, while offering benefits in comparison to highly absorbent swabs in terms comfort, limited volume collection, and potential multiple usage.
Neutralizing Antibody Response to Pseudotype SARS-CoV-2 Differs between mRNA-1273 and BNT162b2 COVID-19 Vaccines and by History of SARS-CoV-2 Infection
Authors: Tyner Harmony L. , Burgess Jefferey L , Grant Lauren , Gaglani Manjusha , Kuntz Jennifer L. , Naleway Allison L. , Thornburg Natalie J. , Caban-Martinez Alberto J. , Yoon Sarang K. , Herring Meghan K. , Beitel Shawn C. , Blanton Lenee , Nikolich-Zugich Janko , Thiese Matthew S. , Pleasants Jessica Flores , Fowlkes Ashley L. , Lutrick Karen , Dunnigan Kayan , M.Yoo Young , Rose Spencer , Groom Holly , Meece Jennifer , Wesley Meredith G. , Schaefer-Solle Natasha , Louzado-Feliciano Paola , Edwards Laura J. , Olsho Lauren E. W. , Thompson Mark G. 
Published: October 2021

ABSTRACTBackgroundData on the development of neutralizing antibodies against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with messenger RNA (mRNA) COVID-19 vaccines are limited.MethodsFrom a prospective cohort of 3,975 adult essential and frontline workers tested weekly from August, 2020 to March, 2021 for SARS-CoV-2 infection by Reverse Transcription- Polymerase Chain Reaction (RT-PCR) assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum- neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t-tests and linear mixed effects models.ResultsAmong 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed neutralizing antibodies (nAb) with a GMT of 1,003 (95% CI=766-1,315). Among 139 previously uninfected participants, 138 (99%) developed nAb after mRNA vaccine dose-2 with a GMT of 3,257 (95% CI = 2,596-4,052). GMT was higher among those receiving mRNA-1273 vaccine (GMT =4,698, 95%CI= 3,186-6,926) compared to BNT162b2 vaccine (GMT=2,309, 95%CI=1,825-2,919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21,655 (95%CI=14,766-31,756) after mRNA vaccine dose-1, without further increase after dose- 2.ConclusionsA single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAb to SARS-CoV-2 than after one dose of vaccine or SARS- CoV-2 infection alone. Neutralizing antibody response also differed by mRNA vaccine product.Main Point SummaryOne dose of mRNA COVID-19 vaccine after previous SARS-CoV-2 infection produced the highest neutralizing antibody titers; among those without history of infection, two doses of mRNA vaccine produced the most robust response.
Lower RNA expression of ALDH1A1 distinguishes the favorable risk group in acute myeloid leukemia
Authors: Dancik Garrett M. , Voutsas Ioannis F. , Vlahopoulos Spiros 
Published: October 2021

AbstractThe expression and activity of enzymes that belong to the aldehyde dehydrogenases is a characteristic of both normal and malignant stem cells. ALDH1A1 is an enzyme critical in cancer stem cells. In acute myeloid leukemia (AML), ALDH1A1 protects leukemia-initiating cells from a number of antineoplastic agents, which include inhibitors of protein tyrosine kinases. Furthermore, ALDH1A1 proves vital for the establishment of human AML xenografts in mice. We review here important studies characterizing the role of ALDH1A1 in AML and its potential as a therapeutic target. We also analyze datasets from leading studies, and show that decreased ALDH1A1 RNA expression consistently characterizes the AML patient risk group with a favorable prognosis, while there is a consistent association of high ALDH1A1 RNA expression with high risk and poor overall survival. Our review and analysis reinforces the notion to employ both novel as well as existing inhibitors of the ALDH1A1 protein against AML.
COVID-19 breakthrough infections and pre-infection neutralizing antibody
Authors: Yamamoto Shohei , Maeda Kenji , Matsuda Kouki , Tanaka Akihito , Horii Kumi , Okudera Kaori , Takeuchi Junko S. , Mizoue Tetsuya , Konishi Maki , Ozeki Mitsuru , Sugiyama Haruhito , Aoyanagi Nobuyoshi , Mitsuya Hiroaki , Sugiura Wataru , Ohmagari Norio 
Published: October 2021

AbstractBackgroundWhile increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infections. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity.MethodsWe described incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2,473 fully vaccinated staff (BNT162b2) for breakthrough infection and selected three matched controls. We measured pre-infection neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the two groups.ResultsNo COVID-19 cases occurred 1–2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2–4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and had returned to work early. There was no measurable difference between cases and controls in pre-infection neutralizing antibody titers against the wild-type, Alpha, and Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type.ConclusionsPre-infection neutralizing antibody titers were not decreased among patients with breakthrough infection under the Delta variant rampage. The result points to the importance of infection control measures in the post-vaccination era, irrespective of immunogenicity profile.
“My friends would believe my word”: appropriateness and acceptability of respondent-driven sampling in recruiting young tertiary student men who have sex with men for HIV/STI research in Nairobi, Kenya
Authors: Mwaniki Samuel Waweru , Kaberia Peter Mwenda , Mugo Peter Mwangi , Palanee-Phillips Thesla 
Published: October 2021

AbstractBackgroundTertiary student men who have sex with men (TSMSM) may engage in behaviors that increase their risk of infection with human immunodeficiency virus (HIV) and sexually transmitted infections (STI). Respondent-driven sampling (RDS) has become a popular method for discretely recruiting marginalized populations into HIV/STI research. We conducted formative research to assess appropriateness and acceptability of RDS in recruiting TSMSM into a prospective HIV/STI bio-behavioral survey in Nairobi, Kenya.MethodsBetween September and October 2020, semi-structured qualitative interviews were held with service providers from organizations that serve MSM (n=3), and TSMSM (n=13). Interviews explored social networks of TSMSM, acceptability of using RDS as a sampling method, potential RDS implementation challenges, and proposed solutions to these challenges. Interviews were done in English, audio-recorded and transcribed then analyzed thematically using NVivo version 11.ResultsService providers reflected that TSMSM had large though concealed networks, thus making RDS an appropriate sampling method. Risk of ineligible persons attempting to participate due to the associated double incentive was noted, and using student identification documents as part of eligibility screening recommended. TSMSM also perceived RDS to be an acceptable strategy based on their large social network sizes (10-40), and the trust amongst themselves. TSMSM were concerned about participating due to the risk of being outed as MSM, seeing as same sex behavior is criminalized in Kenya, and hence emphasized that researchers needed to assure them of their confidentiality, and include MSM as part of the study team to encourage participation. TSMSM suggested coupons should indicate value of reimbursement, be pocket-sized and placed in an envelope to avoid loss, and provide directions to and contacts of the survey site for easy access.ConclusionRDS was perceived as both an appropriate and acceptable sampling method. Anticipated challenges of RDS implementation were highlighted, and possible solutions to these challenges suggested.
On Multiply Robust Mendelian Randomization (MR2) With Many Invalid Genetic Instruments
Authors: Sun Baoluo , Liu Zhonghua , Tchetgen Eric Tchetgen 
Published: October 2021

AbstractMendelian randomization (MR) is a popular instrumental variable (IV) approach, in which genetic markers are used as IVs. In order to improve efficiency, multiple markers are routinely used in MR analyses, leading to concerns about bias due to possible violation of IV exclusion restriction of no direct effect of any IV on the out-come other than through the exposure in view. To address this concern, we introduce a new class of Multiply Robust MR (MR2) estimators that are guaranteed to remain consistent for the causal effect of interest provided that at least one genetic marker is a valid IV without necessarily knowing which IVs are invalid. We show that the proposed MR2 estimators are a special case of a more general class of estimators that remain consistent provided that a set of at least k† out of K candidate instrumental variables are valid, for k†≤ K set by the analyst ex ante, without necessarily knowing which IVs are invalid. We provide formal semiparametric theory supporting our results, and characterize the semiparametric efficiency bound for the exposure causal effect which cannot be improved upon by any regular estimator with our favorable robustness property. We conduct extensive simulation studies and apply our methods to a large-scale analysis of UK Biobank data, demonstrating the superior empirical performance of MR2 compared to competing MR methods.
The Omega-3 Index is Inversely Associated with the Neutrophil-Lymphocyte Ratio in Adults
Authors: McBurney Michael I. , Tintle Nathan L. , Harris William S. 
Published: October 2021

SummaryThe neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and measures innate-adaptive immune system balance. The omega-3-index (O3I) measures the amount of EPA+DHA in blood. Both a low O3I and an elevated NLR are associated with increased risk for chronic disease and mortality, including cardiovascular diseases and cancer. Hypothesizing that low O3I may partly contribute to systemic chronic inflammation, we asked if a relationship existed between O3I and NLR in healthy adults (≥18y, n=28,871, 51% female) without inflammation [C-reactive protein (CRP) <3mg/mL)] who underwent a routine clinical assessment. NLR was inversely associated with O3I before (p<0.0001) and after adjusting for age, sex, BMI, and CRP (p<0.0001). Pearson correlations of other variables with NLR were r=0.06 (CRP), r=0.14 (age), and r=0.01(BMI). In this healthy population, an O3I <6.6% was associated with increasing NLR whereas NLR remained relatively constant (low) when O3I >6.6%, suggestive of a quiescent, balanced immune system.
Circulating Tumor-Derived Extracellular Vesicles Predict Clinical Outcomes in11C Choline-identified Oligometastatic Castration-Refractory Prostate Cancer Treated with Stereotactic Ablative Radiotherapy
Authors: Lucien F. , Kim Y. , Qian J , Zhang H. , Arafa A , Abraha F. , Thapa I. , Tryggestad E. J. , Harmsen W. S. , Kosti J. , Ali H. , Orme J. J. , Lowe V. J. , Johnson G. B. , Kwon E. D. , Dong H. , Park S. S. 
Published: October 2021

AbstractStereotactic ablative radiotherapy (SABR) has demonstrated clinical benefit in oligometastatic prostate cancer patients. However, the risk of developing new distant metastatic lesions remains high and only a minority of patients experience durable progression-free response. Therefore, there is a critical need to identify which subset of oligometastatic patients will benefit from SABR alone versus combination SABR and systemic agents. Herein, we provide the first proof-of-concept for the clinical value of circulating prostate cancer-specific extracellular vesicles (PCEVs) as non-invasive predictor of oncological outcomes in oligometastatic castration-refractory prostate cancer (oCRPC) patients treated with SABR.We have defined PCEVs and analyzed their kinetics in the peripheral blood of 79 oCRPC patients with nanoscale flow cytometry at baseline and days 1, 7, and 14 post-SABR. High PCEV levels at baseline was predictive of shorter time to distant recurrence (3.5 vs 6.6 months, p=0.0087). Following SABR, PCEV levels reached a peak at day 7 and median overall survival was significantly longer in patients with higher PCEV levels (32.7 vs 27.6 months, p=0.003). This suggests that pre-treatment PCEV levels can be a biomarker of tumor burden while early changes post-treatment can predict response to SABR. In contrast, radiomic analyses of11C-choline PET/CT before and after SABR was not predictive of clinical outcomes. Interestingly, a correlation was noted between PCEV levels and peripheral tumor-reactive CD8 T cells (TTR; CD8+CD11ahigh).This original study demonstrates that circulating PCEVs can serve as prognostic and predictive marker to SABR in order to identify “true” oCRPC patients. In addition, we provide novel insights in the global crosstalk mediated by PCEVs between tumors and immune cells which leads to systemic suppression of immunity against CRPC. This work lays the foundation for future studies that investigate the underpinnings of metastatic progression and providing new therapeutic targets (e.g PCEVs) to improve SABR efficacy and clinical outcomes in treatment resistant CRPC.
Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern in Children: A Single-Center Retrospective Cohort Study
Authors: Edward Priya R. , Lorenzo-Redondo Ramon , Reyna Megan E. , Simons Lacy M. , Hultquist Judd F. , Patel Ami B. , Ozer Egon A. , Muller William J. , Heald-Sargent Taylor , McHugh Matthew , Dean Taylor J. , Dalal Raj M. , John Jordan , Manz Shannon C. , Kociolek Larry K. 
Published: October 2021

AbstractBackgroundRecent surges in coronavirus 2019 disease (COVID-19) is attributed to the emergence of more transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs). However, the relative severity of SARS-CoV-2 VOCs in children is unknown.MethodsThis retrospective single-center cohort study was performed at the Ann & Robert H. Lurie Children’s Hospital of Chicago, academic free-standing children’s hospital. We included all children ≤ 18 years-old diagnosed with COVID-19 between October 15th, 2020 and August 31st, 2021 and whose SARS-CoV-2 isolate was sequenced using the Illumina platform. For each patient sample, we identified the SARS-CoV-2 lineage, which was assigned to one of the following groups: Non-VOC, alpha VOC, beta VOC, gamma VOC, or delta VOC. We measured frequency of 5 markers of COVID-19 severity: hospitalization; COVID-19 pharmacologic treatment; respiratory support; intensive care unit admission; and severe disease as classified by the COVID-19 World Health Organization (WHO) Clinical Progression Scale (severe disease; score ≥ 6). A series of logistic regression models were fitted to estimate odds of each severity marker with each VOC (in comparison to non-VOCs), adjusting for COVID-19 community incidence and demographic and clinical co-variates.ResultsDuring the study period, 2,025 patients tested positive for SARS-CoV-2; 1,422 (70.2%) had sufficient viral load to permit sequencing. Among the 499 (35.1%) patients whose isolate was sequenced, median (inter-quartile range) age was 7 (1,12) years; 256 (51.3%) isolates were a VOC: 96 (37.5%) alpha, 38 (14.8%) gamma, and 119 (46.5%) delta. After adjusting for age, Black race, Hispanic ethnicity, high-risk medical conditions, and COVID-19 community incidence, neither alpha nor delta was associated with severe COVID-19. Gamma was independently associated with hospitalization (OR 5.9, 95% CI 1.6-21.5, p=0.007), respiratory support (OR 8.3, 95% CI 1.5-56.3, p=0.02), and severe disease as classified by the WHO Clinical Progression Scale (OR 7.7, 95% CI 1.0-78.1, p=0.05).ConclusionsCompared to non-VOC COVID-19 infections, the gamma VOC, but not the alpha or delta VOCs, was associated with increased severity. These data suggest that recent increased in pediatric COVID-19 hospitalizations are related to increased delta COVID-19 incidence rather than increased delta virulence in children.
Interoperability in NHS Acute Trusts within England: a Situation and Capability Analysis using Freedom of Information requests
Authors: Budhdeo Sanjay , Weerasuriya Chathika K , Zhang Joe , Thomas John P , Mariam Neethu , Sharma Nikhil , Cosco Theodore D , Harrison Oliver T , Banerjee Amitava 
Published: October 2021

AbstractBackgroundMany central initiatives to improve digital maturity and interoperability in the NHS started after 2015. There are few prior assessments of digital maturity and interoperability.MethodsFreedom of Information Act requests were sent to all English Acute NHS Trusts and Clinical Commissioning Groups (CCGs) to obtain information regarding digital maturity according to the Healthcare Information and Management Systems Society (HIMSS) Electronic Medical Record Adoption Mode (EMRAM) scale, and interoperability.ResultsOne third of Acute NHS Trusts have an EMR that meets requirements for EMRAM stage 6 or above. 17.4% of responding Trusts considered this. 59.1% of responding Trusts stated that their EMR allows for functional interoperability with other (interoperable) EMRs. The majority of responding Trusts had not conferred with other Trusts when making EMR purchasing decisions.DiscussionIn order to realise the benefits of digitisation and interoperability, we discuss policy recommendations including actions for local health economies.
State-of-the-art EEG artifact removal evaluation
Authors: Jin Zhenyu 
Published: October 2021

AbstractObjectElectroencephalography (EEG) signals suffer from a low signal-to-noise ratio and are very susceptible to muscular, ambient noise, and other artifacts. Many artifact removal algorithms have been proposed to address this problem. However, the evaluation of these algorithms is conventionally too indirect (e.g., black-box comparisons of brain-computer interface performance before and after removal) because it is unclear which part of the signal represents raw EEG and which is noise. This project objectively benchmarks popular artifact removal algorithms and evaluates the fundamental Independent Component Analysis (ICA) approach thanks to a unique dataset where EEG is recorded simultaneously with other physiological signals-facial electromyography (EMG), accelerometers, and gyroscope-while ten subjects perform several repetitions of common artifact-inflicting tasks (blinking, speaking, etc.).ApproachI have compared the correlation between EEG signals and the artifact-representing channels before and after applying an artifact removal algorithm across the different artifact-inflicting tasks. The extent to which an artifact removal method can reduce this correlation objectively quantifies its effectiveness for the different artifacts. In the same direction, I have determined to what extent ICA successfully detects artefactual components in EEG by comparing the corresponding correlations for independent components that are labelled as artifacts with those labeled as EEG.Main resultThe FORCe was found to be the most effective and generic artifact removal method, cleaning almost 40% of artifacts. ICA is shown to be able to isolate almost 70% of artefactual components.SignificanceThis work alleviates the problem of unreliable evaluation of EEG artifact removal frameworks and provides the first reliable benchmark for the most popular algorithms in this literature.
Predicting willingness to be vaccinated for Covid-19: evidence from New Zealand
Authors: Kaine Geoff , Wright Vic , Greenhalgh Suzie 
Published: October 2021

AbstractGovernments around the world are seeking to slow the spread of Covid-19 and reduce hospitalisations by encouraging mass vaccinations for Covid-19. The success of this policy depends on most of the population accepting the vaccine and then being vaccinated. Understanding and predicting the motivation of individuals to be vaccinated is, therefore, critical in assessing the likely effectiveness of a mass vaccination programme in slowing the spread of the virus.In this paper we draw on the I3Response Framework to understand and predict the willingness of New Zealanders to be vaccinated for Covid-19. The Framework differs from most studies predicting willingness to be vaccinated because it is based on the idea that the willingness to adopt a behaviour depends on both involvement (a measure of motivational strength) with the behaviour and attitudes towards the behaviour. We show that predictions of individuals’ willingness to be vaccinated are improved using involvement and attitudes together, compared to attitudes alone. This result has important implications for the implementation of mass vaccination programmes for Covid-19.